Identification and structural analysis of the Schizosaccharomyces pombe SMN complex.

Jyotishman Veepaschit,Clemens Grimm,Rémy Bordonné,Utz Fischer,Aravindan Viswanathan

doi:10.1093/nar/gkab158

Jyotishman Veepaschit, Clemens Grimm + Show 3 more

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https://doi.org/10.1093/nar/gkab158

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Abstract

The macromolecular SMN complex facilitates the formation of Sm-class ribonucleoproteins involved in mRNA processing (UsnRNPs). While biochemical studies have revealed key activities of the SMN complex, its structural investigation is lagging behind. Here we report on the identification and structural determination of the SMN complex from the lower eukaryote Schizosaccharomyces pombe, consisting of SMN, Gemin2, 6, 7, 8 and Sm proteins. The core of the SMN complex is formed by several copies of SMN tethered through its C-terminal alpha-helices arranged with alternating polarity. This creates a central platform onto which Gemin8 binds and recruits Gemins 6 and 7. The N-terminal parts of the SMN molecules extrude via flexible linkers from the core and enable binding of Gemin2 and Sm proteins. Our data identify the SMN complex as a multivalent hub where Sm proteins are collected in its periphery to allow their joining with UsnRNA.

Highlights

The genetic information of the cell is stored in the form of Deoxyribonucleic acid (DNA) in the nucleus
The Sm proteins and the uridine rich small nuclear ribonucleic acid (UsnRNA) assemble into mature Sm-core particles by an assisted assembly process and are imported back into the nucleus where they dissociate from the assembly factors and are targeted to cajal bodies for further maturation steps
The late cytoplasmic phase involves the action of the SMN complex which removes the assembly chaperone induced kinetic trap and loads the Sm protein intermediates onto the Sm-site of UsnRNA, leading to the generation of the mature Sm-core

Summary

Introduction

The genetic information of the cell is stored in the form of Deoxyribonucleic acid (DNA) in the nucleus. All protein coding genes are first transcribed by the RNA polymerase II through a complex transcription process within the nucleus This results in the production of a primary messenger RNA transcripts (pre-mRNAs) containing both exons and introns. Through a process called splicing, the introns are excised from pre-mRNA transcripts and the exons ligated to produce the mature mRNA, generating an open reading frame for the translation into a given protein. This process is facilitated by the action of the splicing machinery termed spliceosome, which recognizes specific cis-acting elements at the exon-intron boundaries as well as within the intronic and exonic regions (Wahl et al 2009)

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