Most lncRNAs are Junk and lncRNA Papers are Hype

A new paper titled ‘Non-coding RNA: what is functional and what is junk?’ came out recently, reviewing all spectacular claims about mammalian genome being filled with long noncoding RNAs (h/t: @tryangregory). The last sentence of the abstract summarizes it all -

“Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk.”

Here is the full abstract -

The genomes of large multicellular eukaryotes are mostly comprised of non- protein coding DNA. Although there has been much agreement that a small fraction of these genomes has important biological functions, there has been much debate as to whether the rest contributes to development and/or homeostasis. Much of the speculation has centered on the genomic regions that are transcribed into RNA at some low level. Unfortunately these RNAs have been arbitrarily assigned various names, such as intergenic RNA, long non-coding RNAs, etc., which have led to some confusion in the field. Many researchers believe that these transcripts represent a vast, unchartered world of functional non-coding RNAs (ncRNAs), simply because they exist. However, there are reasons to question this Panglossian view because it ignores our current understanding of how evolution shapes eukaryotic genomes and how the gene expression machinery works in eukaryotic cells. Although there are undoubtedly many more functional ncRNAs yet to be discovered and characterized, it is also likely that many of these transcripts are simply junk. Here we discuss how to determine whether any given ncRNA has a function. Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk.

The paper is well worth reading, but if you are too busy with ENCODE committee meetings, Dan Graur is here to help -

So, listen badly trained technicians, especially those working with lncRNA. To prove that your sequence is functional in a meaningful evolutionary manner, you have show that the sequence is either maintained by purifying selection or by positive selection (or some other type of selection). You cannot base your claims of functionality on performance of a certain biochemical reaction. It is the same with shoes; the binding of chewing gum to shoe soles does not prove that this is the function of shoes.

The function of very expensive shoes is NOT to bind chewing gum