The Ribosome Cooperates with the Assembly Chaperone pICln to Initiate Formation of snRNPs

Elham Paknia,Ashwin Chari,Holger Stark,Utz Fischer

doi:10.1016/j.celrep.2016.08.047

Abstract

The formation of macromolecular complexes within the crowded environment of cells often requires aid from assembly chaperones. PRMT5 and SMN complexes mediate this task for the assembly of the common core of pre-mRNA processing small nuclear ribonucleoprotein particles (snRNPs). Core formation is initiated by the PRMT5-complex subunit pICln, which pre-arranges the core proteins into spatial positions occupied in the assembled snRNP. The SMN complex then accepts these pICln-bound proteins and unites them with small nuclear RNA (snRNA). Here, we have analyzed how newly synthesized snRNP proteins are channeled into the assembly pathway to evade mis-assembly. We show that they initially remain bound to the ribosome near the polypeptide exit tunnel and dissociate upon association with pICln. Coincident with its release activity, pICln ensures the formation of cognate heterooligomers and their chaperoned guidance into the assembly pathway. Our study identifies the ribosomal quality control hub as a site where chaperone-mediated assembly of macromolecular complexes can be initiated.

Highlights

Recent systematic interaction profiling of the proteome revealed a strong modularity, where most proteins and/or nucleic acids are incorporated into complexes (Gavin et al, 2006)
In some cases, the number of trans-acting assembly factors exceeds the number of parts to be assembled, as exemplified for the common Sm/Lsm core structure of the pre-mRNA processing small nuclear ribonucleoprotein particles (Fischer et al, 2011)
We first focused on the assembly of the U7 small nuclear ribonucleoprotein particles (snRNPs) core particle, which consists of the Sm proteins B, D3, E, F, and G, as well as the Lsm10/Lsm11 heterodimer

Summary

Introduction

Recent systematic interaction profiling of the proteome revealed a strong modularity, where most proteins and/or nucleic acids are incorporated into complexes (Gavin et al, 2006). These complexes, on average, contain ten subunits and are composed of proteins alone or proteins and nucleic acids (Gavin et al, 2006). The formation of macromolecular complexes in vivo, in many cases, depends on trans-acting factors, which sequester individual subunits and safeguard them until incorporated into higher order assemblies (Chari and Fischer, 2010). In some cases, the number of trans-acting assembly factors exceeds the number of parts to be assembled, as exemplified for the common Sm/Lsm core structure of the pre-mRNA processing small nuclear ribonucleoprotein particles (snRNPs) (Fischer et al, 2011)

Results

Discussion

Conclusion