Ribosome Associated Protein Quality Control: Mechanism and Function

Abstract

Due to numerous reasons, including faulty m RNA, insufficient availability of charged t RNA, genetic errors, ribosomes are failed to synthesize protein sometimes. All organisms develop their machinery to recognize stalled ribosomes. Stalled ribosomes, results in the production of a truncated polypeptide which can affect cells. So, they must be eliminated, by mechanisms known as Ribosome-associated protein quality control (RQC). E3 ubiquitin ligase Ltn1 in RQC promotes clearance of 60S subunit and targets aberrant nascent polypeptides for proteasomal degradation. In eukaryotes, RQC facilitates the ribosomal rescue, where staled m RNAs release and allow to degrade and ribosomal subunits are to be recycled for further use. Ribosome-associated protein quality control in yeast is accomplished by Hel2-dependent ubiquitination of uS10 and RQC-trigger (RQT) complex. RQC in a mammal is done by ZNF598-dependent ubiquitination of collided ribosomes, which also activates signal integrator 3, a component of the ASCC complex. Human RQT (h RQT) is made up of ASCC3, ASCC2, TRIP4, which are orthologs of RNA helicase Slh1, ubiquitin-binding protein Cue3, and ykR023W protein respectively. Ubiquitin-binding activity and ATPase activity of ASCC2 and ASCC3 respectively, are important for RQC. So, it is obvious that the h RQT complex recognizes the ubiquitinated defective ribosome and induces subunit dissociation for RQC. Biogenesis of new polypeptide, folding, correct localization are the fundamental processes to maintain proteostasis, which involve various factors directly attached with ribosomes and chaperones. Ribosome-associated protein biogenesis factors mediate the cellular proteostasis network to form integrity.