The RNA-binding protein PRRC2B preserves 5' TOP mRNA during starvation to maintain ribosome biogenesis during 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' TOP mRNAs under conditions of mTOR inhibition. We discovered that like LARP1, PRRC2B is an important regulator of 5' TOP mRNA levels during starvation, particularly those encoding ribosomal proteins. Overall, our study elucidates a newly discovered function for PRRC2B as an RNA-binding protein that regulates ribosomal biogenesis, establishing it as a global regulator of translation in addition to its function in initiating specific target translation.