Saturday, November 05, 2022

Nature journalist is confused about noncoding RNAs and junk

Nature Methods is one of the journals in Nature Portfolio published by Springer Nature. Its focus is novel methods in the life sciences.

The latest issue (October, 2022) highlights the issues with identifying functional noncoding RNAs and the editorial, Decoding noncoding RNAs, is quite good—much better than the comments in other journals. Here's the final paragraph.

Despite the increasing prominence of ncRNA, we remind readers that the presence of a ncRNA molecule does not always imply functionality. It is also possible that these transcripts are non-functional or products from, for example, splicing errors. We hope this Focus issue will provide researchers with practical advice for deciphering ncRNA’s roles in biological processes.

However, this praise is mitigated by the appearance of another article in the same journal. Science journalist, Vivien Marx has written a commentary with a title that was bound to catch my eye: How noncoding RNAs began to leave the junkyard. Here's the opening paragraph.

Junk. In the view of some, that’s what noncoding RNAs (ncRNAs) are — genes that are transcribed but not translated into proteins. With one of his ncRNA papers, University of Queensland researcher Tim Mercer recalls that two reviewers said, “this is good” and the third said, “this is all junk; noncoding RNAs aren’t functional.” Debates over ncRNAs, in Mercer’s view, have generally moved from ‘it’s all junk’ to ‘which ones are functional?’ and ‘what are they doing?’

This is the classic setup for a paradigm shaft. What you do is create a false history of a field and then reveal how your ground-breaking work has shattered the long-standing paradigm. In this case, the false history is that the standard view among scientists was that ALL noncoding RNAs were junk. That's nonsense. It means that these old scientists must have dismissed ribosomal RNA and tRNA back in the 1960s. But even if you grant that those were exceptions, it means that they knew nothing about Sidney Altman's work on RNAse P (Nobel Prize, 1989), or 7SL RNA (Alu elements), or the RNA components of spliceosomes (snRNAs), or PiWiRNAs, or snoRNAs, or microRNAs, or a host of regulatory RNAs that have been known for decades.

Knowledgeable scientists knew full well that there are many functional noncoding RNAS and that includes some that are called lncRNAs. As the editorial says, these knowledgeable scientists are warning about attributing function to all transcripts without evidence. In other words, many of the transcripts found in human cells could be junk RNA in spite of the fact that there are also many functional nonciding RNAs.

So, Tim Mercer is correct, the debate is over which ncRNAs are functional and that's the same debate that's been going on for 50 years. Move along folks, nothing to see here.

The author isn't going to let this go. She decides to interview John Mattick, of all people, to get a "proper" perspective on the field. (Tim Mercer is a former student of Mattick's.) Unfortunately, that perspective contains no information on how many functional ncRNAs are present and on what percentage of the genome their genes occupy. It's gonna take several hundred thousand lncRNA genes to make a significant impact on the amount of junk DNA but nobody wants to say that. With John Mattick you get a twofer: a false history (paradigm strawman) plus no evidence that your discoveries are truly revolutionary.

Nature Methods should be ashamed, not for presenting the views of John Mattick—that's perfectly legitimate—but for not putting them in context and presenting the other side of the controversy. Surely at this point in time (2022) we should all know that Mattick's views are on the fringe and most transcripts really are junk RNA?


7 comments:

  1. Not a typo. I'm not talking about a real paradigm shift. I'm talking about a fake one that pretends to be real - a paradigm shaft.

    ReplyDelete
  2. @Graham Jones

    Thanks. Missed that. Fixed.

    ReplyDelete
  3. And a formatting error: incorrectly closed hyperlink tag after "RNA components of spliceosomes (snRNAs)".

    One of those days, I suppose :-)

    ReplyDelete