Abstract
Long intergenic non-coding RNAs (lincRNAs) represent a large fraction of transcribed loci in the human genome. Although classified as non-coding, the vast majority of lincRNAs contain putative open reading frames (pORFs), and the molecular mechanisms hindering their translation are currently unclear.
Here, we analysed the sequences of lincRNAs in six species, ranging from human to fission yeast. We found that the trinucleotide (“codon”) composition of their pORFs is distinct from that of mRNA. Strikingly, relative to mRNAs and nuclear lincRNAs, pORFs in highly expressed cytosolic lincRNAs tend to use codons corresponding to less frequent tRNAs and are less frequently bound by ribosomes than coding RNA types. For the majority of cytosolic lincRNAs, we found that their variation in ribosome binding across five human cell lines can partially be explained by cell line-specific tRNA abundances.
Our observations are consistent with lincRNA pORFs having adapted their sequences to less abundant tRNAs. We propose that this serves to counteract ribosome binding and translation of cytoplasmic lincRNAs.
Competing Interest Statement
The authors have declared no competing interest.