Rrp6: Integrated roles in nuclear RNA metabolism and transcription termination

Abstract

The yeast RNA exosome is a eukaryotic ribonuclease complex essential for RNA processing, surveillance and turnover. It is comprised of a barrel-shaped core and cap as well as a 3’–5’ ribonuclease known as Dis3 which contains both endo- and exonuclease domains. A second exonuclease, Rrp6, is added in the nucleus. Dis3 and Rrp6 have both shared and distinct roles in RNA metabolism, and this review will focus primarily on Rrp6 and the roles of the RNA exosome in the nucleus. The functions of the nuclear exosome are modulated by cofactors and interacting partners specific to each type of substrate. Generally, the cofactor TRAMP (Trf4/5-Air2/1-Mtr4 polyadenylation) complex helps unwind unstable RNAs, RNAs requiring processing such as rRNAs, tRNAs, or snRNAs or improperly processed RNAs and direct it toward the exosome. In yeast, Rrp6 interacts with Nrd1, the cap binding complex (CBC), and RNA Polymerase II to aid in nascent RNA processing, termination, and polyA tail length regulation. Recent studies have shown that proper termination and processing of short, non-coding RNAs by Rrp6 is particularly important for transcription regulation across the genome and has important implications for regulation of diverse processes at the cellular level. Loss of proper Rrp6 and exosome activity may contribute to various pathologies such as autoimmune disease, neurological disorders, and cancer.

Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum

“…The TRAMP complex is involved in adding short A-tails to e.g. misfolded or improperly processed ncRNAs such as snRNA and tRNAs and thereby target them for degradation by the exosome [65,66]. In Arabidopsis, TRAMP-like and exosome activities have been suggested to be responsible for oligoadenylation and subsequent degradation of intermediates of miRNA biogenesis.…”

Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation

“…In these experiments we included several S. pombe mutants to test whether the derepression of antisense transcription occurs via one of the known defects that occur when S. pombe Spt5 is mutant or depleted, including reduced recruitment of the Paf1 complex (Mbogning et al, 2013) and loss of H3K4 trimethylation (Mbogning et al, 2015; Sanso et al, 2012) (Figure S5A). We also included an spt6-1 mutant, which has greatly elevated levels of antisense transcripts (DeGennaro et al, 2013), and an rrp6 mutant, to test if antisense levels are controlled by the nuclear exosome (Fox and Mosley, 2016). Our results show that for the two genes tested, rif1 + and asn1 + , we detected the 5′ antisense RNAs only when Spt5 is depleted but not in any of the other mutant conditions (Figures 5C, S5B).…”

Survival in Quiescence Requires the Euchromatic Deployment of Clr4/SUV39H by Argonaute-Associated Small RNAs

“…(i) Cells carrying a mutation in exosome components or under certain environmental conditions form heterochromatin domains (HOODs) at several euchromatic regions whose formation requires MTREC, the associated polyA polymerase (Pla1) and polyA binding protein (Pab2), and the nuclear exoribonuclease Dhp1 (Chalamcharla et al, 2015; Lee et al, 2013; Reyes-Turcu et al, 2011; Yamanaka et al, 2013). These RNA surveillance and processing factors, together with other partners, are thought to survey the transcriptome and ensure mRNA quality in wt cells by degrading antisense, cryptic unstable transcripts (CUTs) and aberrant RNAs in the nucleus (Fox and Mosley, 2016). Our sRNA- or H3K9me-enriched gene sets do not show a significant overlap with HOODs.…”

“…Unlike the meiotic H3K9me islands in wt cells, the transcriptional repression of HOODs requires RNAi-dependent heterochromatin formation. These results reveal that the activities of these RNA processing proteins, which enforce mRNA quality control in the nucleus (Fox and Mosley, 2016), limit the availability of euchromatic transcripts as substrates for RNAi proteins in proliferative cells. Also, overexpression of limiting components of the RNAi machinery (such as Dcr1) leads to emergence of RNAi-dependent H3K9me at euchromatic genes (Yu et al, 2014).…”