Functions of the exosome in rRNA, snoRNA and snRNA synthesis

Abstract

C.Allmang and J.Kufel contributed equally to this workThe yeast nuclear exosome contains multiple 3Ј→5Ј exoribonucleases, raising the question of why so many activities are present in the complex. All components are required during the 3Ј processing of the 5.8S rRNA, together with the putative RNA helicase Dob1p/Mtr4p. During this processing three distinct steps can be resolved, and hand-over between different exonucleases appears to occur at least twice. 3Ј processing of snoRNAs (small nucleolar RNAs) that are excised from polycistronic precursors or from mRNA introns is also a multi-step process that involves the exosome, with final trimming specifically dependent on the Rrp6p component. The spliceosomal U4 snRNA (small nuclear RNA) is synthesized from a 3Ј extended precursor that is cleaved by Rnt1p at sites 135 and 169 nt downstream of the mature 3Ј end. This cleavage is followed by 3Ј→5Ј processing of the pre-snRNA involving the exosome complex and Dob1p. The exosome, together with Rnt1p, also participates in the 3Ј processing of the U1 and U5 snRNAs. We conclude that the exosome is involved in the processing of many RNA substrates and that different components can have distinct functions.

The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition

“…19 The exosome is the nucleolus-associated machinery involved in many aspects of RNA quality control and surveillance 31 as well as in rRNA processing. 32 In an Y2H screen, TTRAP was found to bind to a regulatory subunit of yeast analogue of the human exosome (BIND database). It will be interesting to study whether nucleolar cavities are sites for exosome activity and TTRAP might contribute to regulate exosome function.…”

The Roles of Intersubunit Interactions in Exosome Stability

“…The simplest explanation would be that the absence of any of the subunits causes a failure to assemble the whole complex or inactivates it (1). However, it was shown that a yeast strain lacking two exosome subunits showed stronger phenotypes than either single mutant (16), which suggests that the absence of one component does not inactivate the entire complex. In the present work we have studied systematically the effect that the depletion of any of the components of the T. brucei exosome has on the stability of the complex.…”

“…All yeast exosome components are essential for viability, with the exception of Rrp6p, and depletion of each of them yields broadly similar defects in RNA processing (16). Likewise, depletion of all exosome component homologues in T. brucei, with the possible exception of the Csl4p homologue, results in cell death and in very similar defects in 5.8 S rRNA processing (8).…”

Small Nucleolar RNA Clusters in Trypanosomatid Leptomonas collosoma

“…The yeast polycistronic snoRNA precursors are processed by Rnt1p, a homologue of bacterial RNase III (13). The liberated 5Ј and 3Ј ends are further processed by 5Ј 3 3Ј-exonucleases Rat1p and Xrn1p, and the 3Ј 3 5Ј-exosome (including Rrp6p) (14,15).Trypanosomatids are unicellular protozoan parasites that diverged very early from their eukaryotic lineage. These organisms possess unique RNA processing mechanisms such as pre-mRNA trans-splicing and RNA editing (16,17).…”

“…The yeast polycistronic snoRNA precursors are processed by Rnt1p, a homologue of bacterial RNase III (13). The liberated 5Ј and 3Ј ends are further processed by 5Ј 3 3Ј-exonucleases Rat1p and Xrn1p, and the 3Ј 3 5Ј-exosome (including Rrp6p) (14,15).…”