A mutation in the ribosomal protein uS12 reveals novel functions of its universally conserved PNSA loop

Datta, M and Pillai, M and Modak, MJ and Liiv, A and Khaja, FT and Hussain, T and Remme, J and Varshney, U (2020) A mutation in the ribosomal protein uS12 reveals novel functions of its universally conserved PNSA loop. In: Molecular Microbiology . (In Press)

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Abstract

The ribosomal protein uS12 is conserved across all domains of life. Recently, a heterozygous spontaneous mutation in human uS12 (corresponding to R49K mutation immediately downstream of the universally conserved 44PNSA47 loop in Escherichia coli uS12) was identified for causing ribosomopathy, highlighting the importance of the PNSA loop. To investigate the effects of a similar mutation in the absence of any wild-type alleles, we mutated the rpsL gene (encoding uS12) in E. coli. Consistent with its pathology (in humans), we were unable to generate the R49K mutation in E. coli in the absence of a support plasmid. However, we were able to generate the L48K mutation in its immediate vicinity. The L48K mutation resulted in a cold sensitive phenotype and ribosome biogenesis defect in the strain. We show that the L48K mutation impacts the steps of initiation and elongation. Furthermore, the genetic interactions of the L48K mutation with RRF and Pth suggest a novel role of the PNSA loop in ribosome recycling. Our studies reveal new functions of the PNSA loop in uS12, which has so far been studied in the context of translation elongation. © 2020 John Wiley & Sons Ltd

Item Type:	Journal Article
Publication:	Molecular Microbiology
Publisher:	Blackwell Publishing Ltd
Additional Information:	Copyright to this article belongs to Blackwell Publishing Ltd
Keywords:	peptidyl‐tRNA hydrolase ribosomal protein ribosomal subunit ribosome translation fidelity
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	04 Feb 2021 10:32
Last Modified:	04 Feb 2021 10:32
URI:	http://eprints.iisc.ac.in/id/eprint/67894

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