The RNA-binding protein PRRC2B preserves 5′ TOP mRNA during starvation to maintain ribosome biogenesis during nutrient recovery

PRRC2B is an intrinsically disordered RNA-binding protein that is part of the cell's translation machinery. Here, we show that PRRC2B has two alternatively spliced mRNA transcripts producing major long and minor short isoforms. Mass spectrometry-based interaction studies indicated that both isoforms associate with the 40S ribosomal subunit and translation initiation factors. Importantly, the long isoform also interacted with additional RNA-binding proteins through its unique Arg/Gly-rich region. Among these is LARP1, a regulator of 5' terminal oligopyrimidine (TOP) mRNAs under conditions of mTOR inhibition. We discovered that, like LARP1, PRRC2B-long isoform binds to 5' TOP mRNAs. Moreover, it is necessary for the post-transcriptional preservation of their mRNA levels, particularly those encoding ribosomal proteins, during amino acid starvation. In its absence, the rapid de novo translation of ribosomal proteins that takes place upon nutrient recovery is impeded. Overall, our study elucidates a newly discovered function for PRRC2B as an RNA-binding protein that regulates ribosomal biogenesis upon metabolic shift, in addition to its established function in initiating translation of specific mRNA targets.