Mammalian RNA Decay Pathways Are Highly Specialized and Widely Linked to Translation

Abstract

Highlights d Global profiling of mRNA decay pathways and aberrant translation events in mESCs d XRN1 mediates mRNA turnover, whereas SKIV2L acts widely in translation surveillance d AVEN interacts with ribosomes and the Ski complex and counteracts ribosome stalling d Histone mRNAs, uORFs, and small ORFs are key targets of SKIV2L and AVEN

On the Way to Understanding the Interplay between the RNA Structure and Functions in Cells: A Genome-Wide Perspective

“…The direct influence of the structural elements within 3 UTRs on translation remains incompletely discovered, and these structures are usually explored in the context of RNA stability (see below). Nevertheless, the RNA stability and translation efficiency are undeniably inseparable and very often, factors, including 3 UTR binding proteins that control transcript stability and decay, are also engaged in TE regulation [61][62][63].…”

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

“…mRNA splicing and translation were among the highly enriched terms. The cytoplasmic exosome complex is involved in translation-dependent RNA surveillance pathways (Tuck et al, 2020;Schaeffer et al, 2011). Therefore, the enrichment of these GO terms corroborates its functions in RNA metabolism.…”

4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA Decay

“…The reduced cap affinity of 4EHP compared with that of eIF4E (Chapat et al, 2017;Peter et al, 2017;Rom et al, 1998;Zuberek et al, 2007) exposes the mRNA to decapping (Ruscica et al, 2019). A scenario in which the recruitment of deadenylation and decapping factors by GIGYF1/2 occurs co-translationally is in agreement with the ribosomal association and activity of decay factors, such as DDX6 (Sweet et al, 2012), the CCR4-NOT complex (Buschauer et al, 2020), and XRN1 (Pelechano et al, 2015;Tesina et al, 2019;Tuck et al, 2020), and would irreversibly prevent the translation of transcripts with impaired elongation.…”

“…Many of the 4EHP-GIGYF1/2 target mRNAs encode signal peptide (SP)-containing proteins ( Figure 1F) that undergo SRPdependent translocation to the ER. Binding of SRP to the SP transiently interferes with translation elongation and leads to stacking and ribosome collision at the 5 0 end of the CDS (Arpat et al, 2020;Walter and Blobel, 1981;Walter, 1988, 1989).…”