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elife-00777.xml
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<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD v1.1 20151215//EN" "JATS-archivearticle1.dtd">
<!-- UPDATE: eLife is updating to the most recent version of JATS, 1.1
UPDATE: this XML will be used to creat 4 templates for Magazine (Feature) content: Ediotiral, Insight, Feature 1a and Feature 1b-->
<article article-type="article-commentary" dtd-version="1.1"
xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:mml="http://www.w3.org/1998/Math/MathML"
xmlns:xlink="http://www.w3.org/1999/xlink">
<!--
article-commentary - Insight
UPDATE: xmlns:ali="http://www.niso.org/schemas/ali/1.0/" this name space is added in order to add the new license information (see permissions section)
-->
<front>
<journal-meta>
<!-- journal-meta is standard for all articles published by eLife. Can be boilerplate text as this will not change from article to article.
UPDATE: <journal-id journal-id-type="hwp">eLife</journal-id> has been removed - we are no longer hosted by HighWirePress so this is not required -->
<journal-id journal-id-type="nlm-ta">elife</journal-id>
<journal-id journal-id-type="publisher-id">eLife</journal-id>
<journal-title-group>
<journal-title>eLife</journal-title>
</journal-title-group>
<issn pub-type="epub" publication-format="electronic">2050-084X</issn>
<publisher>
<publisher-name>eLife Sciences Publications, Ltd</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">00777</article-id>
<article-id pub-id-type="doi">10.7554/eLife.00777</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Computational and Systems Biology</subject>
</subj-group>
<subj-group subj-group-type="heading">
<subject>Genomics and Evolutionary Biology</subject>
</subj-group>
<!-- @subj-group-type "sub-display-channel" - This is the editorially defined header for this article and it is not from a predefined list.
It is displayed in all caps on the PDF above the title. On the website it prefixes the article title, followed by a colon.-->
<subj-group subj-group-type="sub-display-channel">
<subject>Bioinformatics</subject>
</subj-group>
<!-- @subj-group-type "display-channel" - eLife-defined article type, controlled list: Insight, Editorial, Feature-->
<subj-group subj-group-type="display-channel">
<subject>Insight</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Selecting against accidental RNA interactions</article-title>
</title-group>
<!-- contrib group tagging now to mirror research content exactly, with the exception of new bio section-->
<contrib-group>
<contrib contrib-type="author" corresp="yes" id="author-65580">
<name>
<surname>Corley</surname>
<given-names>Meredith</given-names>
</name>
<contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-4485-5663</contrib-id>
<email>mcorley@email.unc.edu</email>
<xref ref-type="aff" rid="aff1"/>
<xref ref-type="fn" rid="fn1">*</xref>
<xref ref-type="fn" rid="conf1"/>
<!-- bio has been added so the features team have a location to place the textual description of the author, role, affiliation and any thing else.
This will require a new filed in Kriya for them to edit-->
<bio>
<p>Meredith Corley is in the Department of Biology, University of North
Carolina, Chapel Hill, United States. She also likes knitting and has a
dog.</p>
</bio>
</contrib>
<contrib contrib-type="author" corresp="yes" id="author-54862">
<name>
<surname>Laderach</surname>
<given-names>Alain</given-names>
</name>
<contrib-id contrib-id-type="orcid"
authenticated="true">http://orcid.org/0000-0002-5088-9907</contrib-id>
<email>alain@unc.edu</email>
<!-- The <role> tag is used to indicate authors who are eLife Deputy, Senior or Reviewing editors, or members of the eLife staff -->
<role>Reviewing Editor</role>
<xref ref-type="aff" rid="aff1"/>
<xref ref-type="aff" rid="aff2"/>
<xref ref-type="fn" rid="conf2"/>
<!-- bio has been added so the features team have a location to place the textual description of the author, role, affiliation and any thing else.
This will require a new filed in Kriya for them to edit. All <x> tags and punctiation outside the tags has been removed-->
<bio>
<p>Alain Laderach is an eLife Reviewing Editor and is in the Departments of Biology and Chemistry, University
of North Carolina, Chapel Hill, United States. He's chair of something
very important.</p>
</bio>
</contrib>
<!-- 1) equal-contrib="yes" - can only be used if an author contributed equally with another author and this attribute must be present on both their contribs.
There is no limit on the number authors who can have equal contributions and there can be separate groups of equal contribution.
This is linked to a footnote via an xref.
UPDATE: The rid should be equal-contrib1, equal-contrib2 etc to indicate which equal contrib group each author is part of. Even if there is only one
group, the number suffix is still required.-->
<contrib contrib-type="author" id="author-1032" equal-contrib="yes">
<name>
<surname>Schekman</surname>
<given-names>Randy</given-names>
</name>
<role>Editor-in-Chief</role>
<xref ref-type="fn" rid="conf1"/>
<xref ref-type="aff" rid="aff1"/>
<xref ref-type="fn" rid="equal-contrib1">†</xref>
<bio>
<p>Randy Schekman is eLife's Editor-In-Chief and a Howard Hughes Medical Institute investigator.</p>
</bio>
</contrib>
<contrib contrib-type="author" corresp="yes" id="author-17333" equal-contrib="yes">
<name>
<surname>Teare</surname>
<given-names>M Dawn</given-names>
</name>
<email>m.d.teare@sheffield.ac.uk</email>
<role>Reviewing Editor</role>
<xref ref-type="aff" rid="aff1"/>
<xref ref-type="fn" rid="conf1"/>
<xref ref-type="fn" rid="equal-contrib1">†</xref>
<!-- bio has been added so the features team have a location to place the textual description of the author, role, affiliation and any thing else.
This will require a new filed in Kriya for them to edit. All <x> tags and punctiation outside the tags has been removed-->
<bio>
<p>M Dawn Teare is an eLife Reviewing Editor and is in Sheffield School of
Health and Related Research, University of Sheffield, Sheffield, United
Kingdom.</p>
</bio>
</contrib>
<aff id="aff1">
<institution content-type="dept">Department of Biology</institution>
<institution>University of North Carolina</institution>
<addr-line>
<named-content content-type="city">Chapel Hill</named-content>
</addr-line>
<country>United States</country>
</aff>
<aff id="aff2">
<institution content-type="dept">Department of Chemistry</institution>
<institution>University of North Carolina</institution>
<addr-line>
<named-content content-type="city">Chapel Hill</named-content>
</addr-line>
<country>United States</country>
</aff>
</contrib-group>
<author-notes>
<fn fn-type="con" id="equal-contrib1">
<label>†</label>
<p>These authors contributed equally to this work</p>
</fn>
<fn fn-type="fn" id="fn1">
<label>*</label>
<p>A free text footnote for this author</p>
</fn>
</author-notes>
<pub-date date-type="pub" publication-format="electronic">
<day>20</day>
<month>09</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection">
<year>2016</year>
</pub-date>
<volume>5</volume>
<elocation-id>e00777</elocation-id>
<history>
<date date-type="received" iso-8601-date="2016-09-07">
<day>07</day>
<month>09</month>
<year>2016</year>
</date>
<date date-type="accepted" iso-8601-date="2016-09-07">
<day>07</day>
<month>09</month>
<year>2016</year>
</date>
</history>
<permissions>
<copyright-statement>© 2016, Corley and Laderach</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Corley Laderach</copyright-holder>
<ali:free_to_read/>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<ali:license_ref>http://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This article is distributed under the terms of the <ext-link
ext-link-type="uri"
xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative
Commons Attribution License</ext-link>, which permits unrestricted use
and redistribution provided that the original author and source are
credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="elife-00777.pdf"/>
<related-article ext-link-type="doi" id="ra1" related-article-type="commentary-article"
xlink:href="10.7554/eLife.00666"/>
<!-- Abstracts do not have DOIs -->
<abstract>
<p>Random base-pairing interactions between messenger RNAs and noncoding RNAs can
reduce translation efficiency.</p>
</abstract>
<kwd-group kwd-group-type="author-keywords">
<title>Author Keywords</title>
<kwd>ncRNA</kwd>
<kwd>Archaea</kwd>
<kwd>Bacteria</kwd>
<kwd>gene expression</kwd>
<kwd>bioinformatics</kwd>
</kwd-group>
<kwd-group kwd-group-type="research-organism">
<kwd>
<italic>E. coli</italic>
</kwd>
<kwd>Other</kwd>
</kwd-group>
<custom-meta-group>
<custom-meta specific-use="meta-only">
<meta-name>Author impact statement</meta-name>
<meta-value>This is an Insight.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<!-- The key info box only exists for Insights, template 1-->
<boxed-text>
<p><bold>Related research article</bold> Umu SU, Poole AM, Dobson RCJ, Gardner PP.
2016. Avoidance of stochastic RNA interactions can be harnessed to control protein
expression levels in bacteria and archaea. <italic>eLife</italic>
<bold>5</bold>:e13479. doi:<ext-link ext-link-type="uri"
xlink:href="https://dx.doi.org/10.7554/eLife.13479"
>10.7554/eLife.13479</ext-link></p>
<p><bold>Related research article</bold> PM, Mike Boots.
2016. Avoidance of stochastic RNA interactions can be harnessed to control protein
expression levels in bacteria and archaea. <italic>eLife</italic>
<bold>5</bold>:e13479. doi:<ext-link ext-link-type="uri"
xlink:href="https://dx.doi.org/10.7554/eLife.13479"
>10.7554/eLife.13479</ext-link></p>
</boxed-text>
<!-- end of key info box. Only present for template 1 -->
<p>Feature content is different to the research content because it is "magazine"-style and is commissioned.
There are distinct categories of eLife research content with different requirements.</p>
<sec id="s1">
<title>Level 1 heading</title>
<list list-type="bullet">
<list-item>
<p>Editorials</p>
</list-item>
<list-item>
<p>Insights</p>
</list-item>
<list-item>
<p>Features</p>
</list-item>
<list-item>
<p>Research features</p>
</list-item>
</list>
<p>(<xref ref-type="bibr" rid="bib6">Maier et al., 2009</xref>;
<xref ref-type="bibr" rid="bib3">Guo et al., 2008</xref>; <xref ref-type="bibr" rid="bib7">Tuller et al., 2010</xref>; <xref
ref-type="bibr" rid="bib1">Ferreira et al., 2013</xref>; <xref ref-type="bibr"
rid="bib4">Kozak, 2005</xref>; <xref ref-type="bibr" rid="bib2">Gingold and Pilpel,
2011</xref>).</p>
<sec id="s1-1">
<title>Level 2 heading</title>
<list list-type="order">
<list-item>
<p>Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam porttitor venenatis
eros ut pharetra. Suspendisse id urna lacus. Aliquam a interdum sem. Nulla at
scelerisque tellus. Maecenas semper ipsum ut tortor interdum lacinia. Nam
commodo nibh rhoncus justo facilisis, nec finibus justo ultrices. Nam
ullamcorper gravida felis, eu consectetur arcu fringilla nec. Morbi et lorem
erat. Nullam suscipit tellus ac nibh accumsan tincidunt. Praesent ullamcorper,
magna vitae ornare viverra, turpis arcu suscipit odio, at commodo nisi felis non
mi. Cras accumsan justo eget urna maximus egestas.</p>
</list-item>
<list-item>
<p>Interdum et malesuada fames ac ante ipsum primis in faucibus. Vestibulum in
pulvinar leo. Integer nisi erat, blandit et erat ut, auctor pharetra massa.
Vestibulum enim risus, vehicula at fermentum et, accumsan ut lorem. Ut egestas
pretium aliquet. Vestibulum tortor ex, ultrices id eleifend eu, ullamcorper eu
velit. Quisque in est nisi. Vivamus turpis tellus, placerat ac ex vitae,
ullamcorper tincidunt velit. Curabitur sed eros eget ante feugiat auctor. Duis
nec pharetra eros. Maecenas eget dignissim odio. Curabitur tincidunt et massa ut
dignissim. Mauris euismod dui arcu, vel venenatis augue elementum at. Nam
posuere consectetur dignissim. Aliquam erat volutpat. Here is an example of a url reference:
<ext-link ext-link-type="uri" xlink:href="http://imaging.mrc-cbu.cam.ac.uk/statswiki/FAQ/effectSize"
>Link to website</ext-link>.</p>
</list-item>
<list-item>
<p>Morbi volutpat porttitor purus in convallis. In arcu eros, aliquet vel sodales
quis, pellentesque ut dolor. Vivamus efficitur velit in pellentesque pharetra.
Mauris semper dignissim tellus sit amet tempor. Sed sapien nulla, vehicula a
auctor sed, consectetur non nisi. Vestibulum ullamcorper semper diam, ac
lobortis mauris suscipit nec. Pellentesque sollicitudin bibendum tellus sed
euismod. Mauris aliquam laoreet tortor, non luctus dui convallis eu. Cras
fringilla semper placerat. Aenean imperdiet pretium commodo. Pellentesque et sem
viverra turpis convallis faucibus eu et velit. Quisque sed imperdiet turpis,
eget feugiat leo. Maecenas ut aliquet dui. Mauris quis tellus risus.</p>
</list-item>
<list-item>
<p>Etiam arcu ex, porta eget sem vel, varius lobortis sapien. Integer dapibus sed
elit sit amet blandit. Donec tincidunt ante nec posuere vehicula. In purus
tortor, egestas a nibh eu, sollicitudin tincidunt ex. Praesent sodales tempor
purus a imperdiet. Nunc quis ipsum in tortor tristique faucibus ut vel urna.
Etiam a dui vestibulum, blandit purus sed, molestie tortor. Nam imperdiet eget
sem sit amet rutrum. Nullam laoreet fermentum nunc vitae vulputate. Nulla
placerat ornare tincidunt. Donec enim urna, egestas pretium neque ac, vulputate
gravida lacus. Maecenas semper sit amet libero nec maximus.</p>
</list-item>
</list>
<sec id="s1-1-1">
<title>Level 3 heading</title>
<p>This section is present to show there is a level 3 heading required.</p>
</sec>
</sec>
</sec>
<sec id="s2">
<title>Level 1 heading again</title>
<p>Now, in eLife, Paul Gardner of the University of Canterbury and colleagues – including
Sinan Umu (as first author), Anthony Poole and Renwick Dobson – report that the
translation efficiency in bacteria and archaea is influenced by a phenomenon called
"avoidance" (<xref ref-type="bibr" rid="bib8">Umu et al., 2016</xref>). Avoidance is the
degree to which an mRNA molecule avoids random interactions with noncoding RNA molecules
in the cell. Noncoding RNAs, as their name suggests, do not code for proteins, but they
still make up a majority of the RNA in any given cell. Indeed, the researchers show that
the levels of noncoding RNAs in bacterial cells are two orders of magnitude greater than
the levels of mRNAs.</p>
</sec>
<!-- Feature 1 content can contain Tables; no assets in Feature 1 content are assigned DOIs -->
<sec id="s3">
<title>Example of a table</title>
<p>This section has a table in it.</p>
<table-wrap id="table1" position="float">
<label>Table 1.</label>
<caption>
<title>This is the title.</title>
<p>This is the caption: A “snapshot” of the biomedical workforce from 2009.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th/>
<th>Number</th>
<th/>
</tr>
</thead>
<tbody>
<tr>
<td>Biomedical PhD students</td>
<td/>
<td/>
</tr>
<tr>
<td> Total number</td>
<td>83,000</td>
<td/>
</tr>
<tr>
<td> Number who started PhDs</td>
<td>16,000</td>
<td/>
</tr>
<tr>
<td> Number awarded PhDs</td>
<td>9,000</td>
<td/>
</tr>
<tr>
<td> Number who started postdoc</td>
<td>5,800</td>
<td/>
</tr>
<tr>
<td> Average time to PhD (years)</td>
<td>6–7</td>
<td/>
</tr>
<tr>
<td>Post-PhD workforce</td>
<td/>
<td>%</td>
</tr>
<tr>
<td> Scientific research</td>
<td>84,500</td>
<td>66</td>
</tr>
<tr>
<td> <italic>(Government research)</italic></td>
<td>
<italic>(7,000)</italic>
</td>
<td>
<italic>(6)</italic>
</td>
</tr>
<tr>
<td> <italic>(Academic research or teaching)</italic></td>
<td>
<italic>(55,000)</italic>
</td>
<td>
<italic>(43)</italic>
</td>
</tr>
<tr>
<td> <italic>(Industrial research)</italic></td>
<td>
<italic>(22,500)</italic>
</td>
<td>
<italic>(18)</italic>
</td>
</tr>
<tr>
<td> Related to science (not research)</td>
<td>24,000</td>
<td>18</td>
</tr>
<tr>
<td> Unrelated to science</td>
<td>17,000</td>
<td>13</td>
</tr>
<tr>
<td> Unemployed</td>
<td>2,500</td>
<td>2</td>
</tr>
<tr>
<td>Total</td>
<td>128,000</td>
<td>100</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>PhD, doctor of philosophy</p>
</fn>
</table-wrap-foot>
</table-wrap>
<disp-quote>
<p>Ultimately, we ask ourselves: does this manuscript constitute a substantial step
towards a clear answer to an important global health question?</p>
</disp-quote>
<p>To estimate the probability of random base-pairing interactions taking place between
mRNAs and noncoding RNAs, consider a five-base region in a single mRNA. This region can
have any one of a possible 4 <sup>∧</sup> 5=1024 sequences. If the total number of bases
from all the noncoding RNAs in the cell is S, then the number of noncoding RNAs in the
cell that have a perfectly complementary five-base region is approximately S/1024. Umu
et al. studied 325 noncoding RNAs so, assuming an average length of 200 bases for these,
we have S ≈ 325*200 ≈ 65000. Therefore, on average, the number of these noncoding RNAs
that have a five-base region that is perfectly complementary to the five-base region in
the mRNA will be 65000/1024 ≈ 63. Given the number of mRNAs and noncoding RNAs that are
found in cells, random interactions between the two are inevitable. However, if we find
that a given mRNA has base-pairing interactions with fewer noncoding RNAs than expected,
then this is avoidance (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<boxed-text id="box1">
<label>Box 1.</label>
<caption>
<title>Making PhD programmes better and shorter</title>
</caption>
<p>To explore how things might be done differently, let us compare two highly
regarded PhD programmes—the Watson School of Biological Sciences at Cold Spring
Harbor Laboratory (CSHL), and the ‘Tetrad’ program at my own institution, the
University of California, San Francisco (UCSF)—with the average for all graduate
programmes. Two points stand out. First, significantly more of the students
entering the CSHL and UCSF programmes obtained PhDs, and significantly more also
opted for a career in research, which suggests that a large majority of
‘average’ programmes recruit less able students and/or train them poorly.
Second, the time taken to obtain a PhD was notably shorter at CSHL—just 4.6
years, compared with 6.5 years at UCSF and 6–7 years on average.</p>
</boxed-text>
<!-- Assets are not assigned sub-DOIs. -->
<fig id="fig1" position="float">
<label>Figure 1.</label>
<caption>
<title>One column wide. Class A.</title>
<p>This figure should be typeset at the width of one text column.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-00777-fig1.tif"/>
<!-- Where a credit is required for an image, this will be added using the <attrib> tag at the end of the figure block.
This may or may not need to be a clickable link -->
<attrib>Image credit: <ext-link ext-link-type="uri" xlink:href="http://orcid.org/0000-0002-4485-5663">
Meredith Corley</ext-link></attrib>
</fig>
<p>Realistically, RNA binding interactions are governed by thermodynamics and do not always
follow strict pairing rules. Furthermore, RNA molecules can pair with themselves in
intra-molecular interactions and must “unfold” a given region in order to pair with
another molecule. Thus it is important to quantify mRNA-noncoding RNA interactions with
net "binding energy" calculations. The binding energy quantifies the thermodynamics of
RNA base-pairing, with low binding energies indicating very stable interactions. To
explore the phenomenon of avoidance, Umu et al. used a computational RNA interaction
model to estimate the binding energies for interactions between mRNAs and noncoding
RNAs. The RNAs include a core set of 114 mRNAs that are well conserved across bacteria
(including 40 that are also conserved across archaea) and 325 noncoding RNAs from six
families of RNA that are also well conserved across bacterial and archaeal species. </p>
<boxed-text id="box2">
<label>Box 2.</label>
<caption>
<title>Further resources</title>
</caption>
<p>Guidance on how to estimate sample sizes is available from a number of
organizations:</p>
<list list-type="simple">
<list-item>
<p><bold><italic>Equator Network</italic></bold>. <ext-link ext-link-type="uri"
xlink:href="http://www.equator-network.org"
>http://www.equator-network.org</ext-link>
</p>
</list-item>
<list-item>
<p><bold><italic>Medical Research Council: Cognition and Brain Sciences Unit
</italic></bold>. <ext-link ext-link-type="uri"
xlink:href="http://imaging.mrc-cbu.cam.ac.uk/statswiki/FAQ/effectSize"
>http://imaging.mrc-cbu.cam.ac.uk/statswiki/FAQ/effectSize</ext-link>
</p>
</list-item>
<list-item>
<p><bold><italic>National Centre for the Replacement, Refinement and Reduction
of Animals in Research (NC3Rs)</italic></bold>. <ext-link
ext-link-type="uri"
xlink:href="https://www.nc3rs.org.uk/experimental-design"
>https://www.nc3rs.org.uk/experimental-design</ext-link>
</p>
</list-item>
<list-item>
<p><bold><italic>National Institutes of Health</italic></bold>. <ext-link
ext-link-type="uri"
xlink:href="https://www.nih.gov/research-training/rigor-reproducibility/principles-guidelines-reporting-preclinical-research"
>
https://www.nih.gov/research-training/rigor-reproducibility/principles-guidelines-reporting-preclinical-research</ext-link>
</p>
</list-item>
</list>
<p>The <italic>eLife</italic> transparent reporting form is available in both <ext-link
ext-link-type="uri"
xlink:href="http://submit.elifesciences.org/html/transparent_reporting.docx"
>Word</ext-link> and <ext-link ext-link-type="uri"
xlink:href="http://submit.elifesciences.org/html/transparent_reporting.pdf"
>pdf</ext-link> formats.</p>
</boxed-text>
<p>They found that, on average, the interactions between the core noncoding RNAs and mRNAs
were weaker than the interactions between the noncoding RNAs and a control set. In other
words, they found that the average mRNA "avoids" interactions due to less stable pairing
with noncoding RNAs (<xref ref-type="fig" rid="fig1">Figure 1B</xref>; <xref
ref-type="other" rid="video1">Video 1</xref>). This trend holds true for over 70% of
the bacteria and archaea that they tested. There are, of course, noncoding RNAs whose
primary function is to bind to mRNAs, but these were excluded from the study. Instead,
the goal was to observe selection against <italic>accidental</italic> interactions
between mRNAs and the large and diverse set of noncoding RNAs that are resident in the
cell. </p>
<fig id="fig2" position="float">
<label>Figure 2.</label>
<caption>
<title>One column wide and the margin. Class B.</title>
<p>This figure should be typeset at the width of one text column and the margin.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-00777-fig2.tif"/>
</fig>
<fig id="fig3" position="float">
<label>Figure 3.</label>
<caption>
<title>Two column wide. Class C.</title>
<p>This figure should be typeset at the width of both text columns.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-00777-fig3.tif"/>
</fig>
<fig id="fig4" position="float">
<label>Figure 4.</label>
<caption>
<title>Two column wide and the margin. Class D.</title>
<p>This figure should be typeset at the width of both text columns and the margin.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="elife-00777-fig4.tif"/>
</fig>
<!-- Videos: Like figures, they do not have DOIs.
UPDATE: This no longer required for videos: content-type="glencoe play-in-place height-250 width-310" mime-subtype="wmv" mimetype="video"
UPDATE: changed id to videoX -->
<media mimetype="video" mime-subtype="mp4" id="video1" xlink:href="elife-00777-video1.mp4">
<label>Video 1.</label>
<caption>
<title>A description of the eLife editorial process.</title>
</caption>
</media>
<p>Umu et al. hypothesize that avoidance is due to the negative effect that the interactions
between mRNAs and noncoding RNA could have on translation efficiency: for example, if a
noncoding RNA pairs with a start codon in an mRNA, it will prevent translation from
taking place because the ribosome will not be able to bind to that mRNA (<xref
ref-type="fig" rid="fig1">Figure 1C</xref>). To test this hypothesis, the
researchers designed and synthesized a set of mRNAs with sequences that have high levels
of avoidance, and a set of mRNAs with low levels of avoidance. When they measured the
translation efficiency for both sets of mRNAs, they found that it was much higher for
the highly-avoidant set.</p>
<p>Umu et al. also synthesized different sets of mRNAs to explore two other factors that are
thought to influence translation efficiency: codon bias and the intra-mRNA folding
energy (<xref ref-type="bibr" rid="bib5">Kudla et al., 2009</xref>; <xref
ref-type="bibr" rid="bib7">Tuller et al., 2010</xref>). Both factors did cause some
variation in the production of protein, but avoidance was responsible for the most
variation. They also found the same correlation with avoidance when they studied
previously published measurements of bacterial translation efficiency. This suggests
that the ability of an mRNA to avoid interactions with noncoding RNAs is a hitherto
unknown, yet important factor affecting translation efficiency.</p>
<p>One notable aspect of this study is that it relied almost entirely on publicly available
data sets. This underscores the importance of open data for exploring basic biological
questions that apply to many different organisms. Using this data, which no single lab
could have collected alone, Umu et al. have shown that mRNA sequences are optimized to
minimize interactions with noncoding RNAs and have demonstrated why such avoidance is so
desirable. And the need to avoid spurious interactions is not unique to RNA: the
emergence of complex life depends on optimizing molecular interactions that lead to
reproduction in the midst of molecular chaos. Although networks of highly specific
molecular interactions are a hallmark of evolution, in many cases it is just as
important to avoid accidental interactions.</p>
<p>By thinking more carefully and thoroughly about issues like sample sizes, replicates and
statistical analysis, by reporting the results of these considerations more fully, and
by making data and code available, researchers will increase the confidence of other
researchers and the wider world in the robustness and reliability of their published
work.</p>
</sec>
<sec id="s4">
<title>Note</title>
<p>Any footnotes for Feature content are treated as plain text and are not crosslinked anywhere with a sympol.</p>
</sec>
</body>
<back>
<!-- An Acknowledgements section is only occasionally present for Feature 1 content -->
<ack id="ack">
<title>Acknowledgements</title>
<p>We thank all the members of the EASAC Working Group: Goran Hermeren (Sweden), Ursula
Jenal (Switzerland), Hans Klenk (Germany), Andre Knottnerus (The Netherlands), Maria
Masucci (Sweden), John McCauley (UK), Thomas Mettenleiter (Germany), Giorgio Palu
(Italy), Gyorgy Posfai (Hungary), Bert Rima (Ireland), John Skehel (UK), and Simon
Wain-Hobson (France).</p>
</ack>
<fn-group content-type="competing-interest">
<title>Competing interests</title>
<fn fn-type="conflict" id="conf1">
<p>No competing interests declared</p>
</fn>
<fn fn-type="conflict" id="conf2">
<p>Alain Laderach works for a drug company</p>
</fn>
</fn-group>
<ref-list>
<title>References</title>
<ref id="bib1">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ferreira</surname>
<given-names>JP</given-names>
</name>
<name>
<surname>Overton</surname>
<given-names>KW</given-names>
</name>
<name>
<surname>Wang</surname>
<given-names>CL</given-names>
</name>
</person-group>
<year iso-8601-date="2013">2013</year>
<article-title>Tuning gene expression with synthetic upstream open reading
frames</article-title>
<source>PNAS</source>
<volume>110</volume>
<fpage>11284</fpage>
<lpage>11289</lpage>
<pub-id pub-id-type="doi">10.1073/pnas.1305590110</pub-id>
</element-citation>
</ref>
<ref id="bib2">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gingold</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Pilpel</surname>
<given-names>Y</given-names>
</name>
</person-group>
<year iso-8601-date="2011">2011</year>
<article-title>Determinants of translation efficiency and
accuracy</article-title>
<source>Molecular Systems Biology</source>
<volume>7</volume>
<elocation-id>481</elocation-id>
<pub-id pub-id-type="doi">10.1038/msb.2011.14</pub-id>
</element-citation>
</ref>
<ref id="bib3">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Guo</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Xiao</surname>
<given-names>P</given-names>
</name>
<name>
<surname>Lei</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Deng</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Xiao</surname>
<given-names>GG</given-names>
</name>
<name>
<surname>Liu</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Chen</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Li</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Wu</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Chen</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Jiang</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Tan</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Xie</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Zhu</surname>
<given-names>X</given-names>
</name>
<name>
<surname>Liang</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Deng</surname>
<given-names>H</given-names>
</name>
</person-group>
<year iso-8601-date="2008">2008</year>
<article-title>How is mRNA expression predictive for protein expression? A
correlation study on human circulating monocytes</article-title>
<source>Acta Biochimica Et Biophysica Sinica</source>
<volume>40</volume>
<fpage>426</fpage>
<lpage>436</lpage>
<pub-id pub-id-type="doi">10.1111/j.1745-7270.2008.00418.x</pub-id>
</element-citation>
</ref>
<ref id="bib4">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kozak</surname>
<given-names>M</given-names>
</name>
</person-group>
<year iso-8601-date="2005">2005</year>
<article-title>Regulation of translation via mRNA structure in prokaryotes and
eukaryotes</article-title>
<source>Gene</source>
<volume>361</volume>
<fpage>13</fpage>
<lpage>37</lpage>
<pub-id pub-id-type="doi">10.1016/j.gene.2005.06.037</pub-id>
</element-citation>
</ref>
<ref id="bib5">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kudla</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Murray</surname>
<given-names>AW</given-names>
</name>
<name>
<surname>Tollervey</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Plotkin</surname>
<given-names>JB</given-names>
</name>
</person-group>
<year iso-8601-date="2009">2009</year>
<article-title>Coding-sequence determinants of gene expression in Escherichia
coli</article-title>
<source>Science</source>
<volume>324</volume>
<fpage>255</fpage>
<lpage>258</lpage>
<pub-id pub-id-type="doi">10.1126/science.1170160</pub-id>
</element-citation>
</ref>
<ref id="bib6">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Maier</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Güell</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Serrano</surname>
<given-names>L</given-names>
</name>
</person-group>
<year iso-8601-date="2009">2009</year>
<article-title>Correlation of mRNA and protein in complex biological
samples</article-title>
<source>FEBS Letters</source>
<volume>583</volume>
<fpage>3966</fpage>
<lpage>3973</lpage>
<pub-id pub-id-type="doi">10.1016/j.febslet.2009.10.036</pub-id>
</element-citation>
</ref>
<ref id="bib7">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tuller</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Waldman</surname>
<given-names>YY</given-names>
</name>
<name>
<surname>Kupiec</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Ruppin</surname>
<given-names>E</given-names>
</name>
</person-group>
<year iso-8601-date="2010">2010</year>
<article-title>Translation efficiency is determined by both codon bias and
folding energy</article-title>
<source>PNAS</source>
<volume>107</volume>
<fpage>3645</fpage>
<lpage>3650</lpage>
<pub-id pub-id-type="doi">10.1073/pnas.0909910107</pub-id>
</element-citation>
</ref>
<ref id="bib8">
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Umu</surname>
<given-names>SU</given-names>
</name>
<name>
<surname>Poole</surname>
<given-names>AM</given-names>
</name>
<name>
<surname>Dobson</surname>
<given-names>RCJ</given-names>
</name>
<name>
<surname>Gardner</surname>
<given-names>PP</given-names>
</name>
</person-group>
<year iso-8601-date="2016">2016</year>
<article-title>Avoidance of stochastic RNA interactions can be harnessed to
control protein expression levels in bacteria and archaea</article-title>
<source>eLife</source>
<volume>5</volume>
<elocation-id>e13479</elocation-id>
<pub-id pub-id-type="doi">10.7554/eLife.13479</pub-id>
</element-citation>
</ref>
</ref-list>
</back>
</article>