Nuclear sorting of RNA

Mammalian genomes are hyperactive but, paradoxically, a major part of the produced RNA is rapidly degraded. Labile RNAs share common features with their functional counterparts, which motivates the question: Which molecular mechanisms sort nuclear RNAs into stable, functional RNA-protein particles vs. those destined for degradation? We have found that the essential ARS2 protein holds binary functions in RNA maturation and decay. Given its omnipresence on nascent RNA, we hypothesize that transcript fate is governed by the competitive interaction of ARS2 with productive and destructive factors. Through a delineation of the responsible protein complexes and domains, we will expose the underlying molecular logic, both at steady state and in the dynamic context of stem cell differentiation. Our work will disclose the fundamental question of how cells cope with a massive genomic output without erroneously degrading functional RNA or leaving spurious transcripts ignored.