ALYREF links 3′‐end processing to nuclear export of non‐polyadenylated mRNA s

Abstract

The RNA‐binding protein ALYREF plays key roles in nuclear export and also 3′‐end processing of polyadenylated mRNAs, but whether such regulation also extends to non‐polyadenylated RNAs is unknown. Replication‐dependent (RD)‐histone mRNAs are not polyadenylated, but instead end in a stem‐loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD‐histone mRNAs. SL‐binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre‐mRNA 3′‐end processing by facilitating U7‐snRNP recruitment through physical interaction with the U7‐snRNP‐specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3′‐end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3′‐end processing and nuclear export of non‐polyadenylated mRNAs.

TPR is required for the efficient nuclear export of mRNAs and lncRNAs from short and intron-poor genes

“…In particular, histone mRNAs, which are mostly intronless, were the most affected by TPR-depletion (Figure 3E , red data points). Although histone mRNAs undergo unique processing events, these mRNAs require TREX for their export ( 29 , 70 ). Another class of mRNAs that were affected by TPR-depletion were those that encode ribosomal proteins (Figure 3E , yellow data points).…”

“…Nonetheless, TREX components have also been shown to be efficiently loaded onto mRNAs even in the absence of splicing ( 22–26 ). TREX may be recruited by RNA polymerase II in a co-transcriptional manner ( 1 ), by the nuclear cap-binding complex ( 27 ), by exon-splicing elements ( 28 ) and by the 3′ cleavage and polyadenylation machinery ( 29 ). As such, TREX components are required for the export of non-spliced mRNAs ( 22–24 , 28 , 30 ).…”

TPR is required for the nuclear export of mRNAs and lncRNAs from intronless and intron-poor genes

“…In particular, histone mRNAs, which are mostly intronless, were the most affected by TPR-depletion ( Figure 2E). Although histone mRNAs undergo unique processing events, these mRNAs require TREX for their export (28,68). Another class of mRNAs that were affected by TPR-depletion were those that encode ribosomal proteins ( Figure 2E).…”

“…Nonetheless, TREX components have also been shown to be efficiently loaded onto mRNAs even in the absence of splicing (22)(23)(24)(25)(26). TREX may be recruited by RNA polymerase II in a co-transcriptional manner (1), by the nuclear cap-binding complex (27) and by the 3' cleavage and polyadenylation machinery (28). As such, TREX components are required for the export of non-spliced mRNAs (22,23,29).…”

High-throughput siRNA screening reveals functional interactions and redundancies of human processive exoribonucleases

“…Notably, among negative GIs of DIS3L were genes that are involved in RNA transport from the nucleus (THOC2, ALYREF, NUP133, POP1, POP5, and EIF2S2). THOC2 and ALYREF are a part of the TREX complex (Chi et al, 2013), whereas NUP133 is a part of the nuclear pore (Boehmer et al, 2008), and all are involved in mRNP biogenesis and mRNA export (Vasu et al, 2001;Fan et al, 2019). These steps are subject to robust quality control.…”