Sunday, May 20, 2012

Time to Re-write the Textbooks: RNA has a Fifth Base!!!

From Science Daily via a press release from NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College: RNA Modification Influences Thousands of Genes: Revolutionizes Understanding of Gene Expression.
Over the past decade, research in the field of epigenetics has revealed that chemically modified bases are abundant components of the human genome and has forced us to abandon the notion we've had since high school genetics that DNA consists of only four bases.

Now, researchers at Weill Cornell Medical College have made a discovery that once again forces us to rewrite our textbooks. This time, however, the findings pertain to RNA, which like DNA carries information about our genes and how they are expressed. The researchers have identified a novel base modification in RNA which they say will revolutionize our understanding of gene expression.

Their report, published May 17 in the journal Cell, shows that messenger RNA (mRNA), long thought to be a simple blueprint for protein production, is often chemically modified by addition of a methyl group to one of its bases, adenine. Although mRNA was thought to contain only four nucleobases, their discovery shows that a fifth base, N6-methyladenosine (m6A), pervades the transcriptome.
Those who don't know history are destined to repeat it.

Edmund Burke
We've known about modified bases in DNA since the early 1970s so there aren't any modern textbooks that don't mention them. If your high school genetics course didn't mention modified bases it isn't because scientists didn't know of their existence—unless, of course, you graduated from high school more than forty years ago.

We've known about the presence of N6-methyladenosine in mRNA for several decades. Here's the introduction to a 1984 paper by Horowitz et al. (1984).
The most prevalent internal methylated nucleoside in eukaryotic mRNA is N6-methyladenosine (m6A). This modified nucleoside is found in RNAs of higher eukaryotic organisms (1-6), plants (7-9), and viruses (3, 10-12), and occurs at two specific sequences: Gpm6ApC and Apm6ApC (13-17).
Refereences 1-5 are from 1975 meaning that in the published scientific literature the presence of m6A dates back 37 years. That's more than enough time to make it into the textbooks. It's in the textbooks.

Not only that, textbooks also contain references to two other modified bases in mRNA. N7-methylguanylate is common in cap structures and several mRNAs are known to contain inosine (I), a modified form of adenylate.

I blame the science writers at Cornell Medical Center for writing something that is not true and I blame the authors of the paper for hype and exaggeration and for not correcting the press release before it was published. That's not how science is supposed to work.


[Hat Tip: Uncommon Descent: Is there a fifth base in RNA?]

Horowitz, S., Horowitz, A., Nilsen, T.W., Munns, T.W. and Rottman, F.M. (1984) Mapping of N6-methyladenosine residues in bovine prolactin mRNA. PNAS 81:5667-5671. [PDF]


10 comments :

  1. Triple facepalm

    That one ranks among the worst press releases ever - when the paper itself refers to decades of prior work:

    The distribution of m6A in RNA is poorly understood. Previous
    studies have found that m6A exists in RNA from a variety of unique organisms, including viruses, yeast, and mammals (Beemon and Keith, 1977; Bodi et al., 2010). m6 A is found in tRNA (Saneyoshi et al., 1969), rRNA (Iwanami and Brown, 1968), and viral RNA (Beemon and Keith, 1977; Dimock and Stoltzfus, 1977). Although m6 A is detectable in mRNA-enriched RNA fractions (Desrosiers et al., 1974), it has been confirmed in vivo in
    only one mammalian mRNA (Horowitz et al., 1984).

    As does the other paper doing the same thing that just came out:

    http://www.nature.com/nature/journal/v485/n7397/full/nature11112.html

    And, finally, there is this:

    http://www.landesbioscience.com/books/iu/id/2324/?nocache=1296045580

    and many other book-length treatments of the subject...

    ReplyDelete
  2. and I blame the authors of the paper for hype and exaggeration and for not correcting the press release before it was published.

    The assumption being that the authors actually had the ability to edit and/or approve the press release before it was published.

    ReplyDelete
    Replies
    1. Authors can, and should, insist on seeing the press release before it is published. Their reputation depends on it.

      I think that all university press releases should come with a statement that the authors and read the copy and approve its content.

      Even if pre-release approval is not university policy, the authors have certainly seen the published press releases and made no attempt to correct it.

      Delete
    2. I think that all university press releases should come with a statement that the authors and read the copy and approve its content.

      Much of the time the researchers are sent a draft of the press release, will make copious changes, trying to rewrite most of it, and still wind up reading a generally poorly written piece of half digested science. Getting scientists to sign off on something means having them more involved in the writing process which is asking a lot, since they already wrote the paper, for little return, scientists don't read press releases.

      Next, journal embargo restrictions are heavy-handed to start with and scare off a lot of university writers so they wind up either not writing anything until the day the embargo is lifted or not sending the researchers a draft until that day just to play it safe. There's also an unnecessary assumption that the person writing the press release is a science writer or knows any science. Most academics don't even bother to notify their university press office when they have a publication coming out, a testament to the likelihood that most think very little of their university press office. As such many press offices are woefully understaffed.

      My university's policy is that only the press release office employees are allowed to write the release: not the scientists themselves and not even another qualified university staff employee, say a graduate student in another dept or lab. However, they are allowed to use press releases from the science journal or other science institutes and stamp their university name on it, which is hypocritical and unethical.

      Delete
    3. I think that all university press releases should come with a statement that the authors and read the copy and approve its content.

      Much of the time the researchers are sent a draft of the press release, will make copious changes, trying to rewrite most of it, and still wind up reading a generally poorly written piece of half digested science. Getting scientists to sign off on something means having them more involved in the writing process which is asking a lot, since they already wrote the paper, for little return, scientists don't read press releases.

      Next, journal embargo restrictions are heavy-handed to start with and scare off a lot of university writers so they wind up either not writing anything until the day the embargo is lifted or not sending the researchers a draft until that day just to play it safe. There's also an unnecessary assumption that the person writing the press release is a science writer or knows any science. Most academics don't even bother to notify their university press office when they have a publication coming out, a testament to the likelihood that most think very little of their university press office. As such many press offices are woefully understaffed.

      My university's policy is that only the press release office employees are allowed to write the release: not the scientists themselves and not even another qualified university staff employee, say a graduate student in another dept or lab. However, they are allowed to use press releases from the science journal or other science institutes and stamp their university name on it, which is hypocritical and unethical.

      Delete
  3. Wow,a nucleic acid with bases modified by methylation? Stop the press!

    Modified bases seem to be a pretty common topic in bad press releases; as evident in (http://sandwalk.blogspot.com/2009/04/modified-bases-in-dna.html). At least we aren't seeing press releases marvelling about the existence of selenocysteine or selenomethionine...

    ReplyDelete
  4. The only consolation here is that the fabricated hype is not about junk DNA, for once.

    ReplyDelete
  5. Isolation and characterization of N6-methyladenosine from Escherichia coli valine transfer RNA.
    Saneyoshi M, Harada F, Nishimura S.
    Biochim Biophys Acta. 1969 Oct 22;190(2):264-73.

    ReplyDelete
  6. 2011 Adenosine methylation in Arabidopsis mRNA is associated with the 3' end and reduced levels cause developmental defects
    http://www.frontiersin.org/Plant_Genetics_and_Genomics/10.3389/fpls.2012.00048/abstract

    2010 Yeast targets for mRNA methylation
    http://nar.oxfordjournals.org/content/38/16/5327.abstract

    2008 MTA Is an Arabidopsis Messenger RNA Adenosine Methylase and Interacts with a Homolog of a Sex-Specific Splicing Factor
    http://www.plantcell.org/content/20/5/1278.abstract

    ReplyDelete
  7. A few weeks ago, Larry posted this comment at Jonathan Eisen’s blog Tree of Life regarding scientific press releases:

    All authors of the paper in question have to agree to the content of the press release and there should be a statement at the bottom of the press release naming each author and saying that they specifically approve the content.

    I think the vast majority of scientists and science writers would agree with this solution on how to fix the increasing flow of deceiving press releases and misleading science communications. However, without a way of bringing this recommendation to their attention and that of the institutions writing these press releases and science communications, this flow will continue.

    A potential solution would be for bloggers to join forces and promote this recommendation. Would that be possible?

    ReplyDelete