Biology subjects

Shanmuganathan, V.

Publications and source records attributed to Shanmuganathan, V..

3 recordsLinked to original sources

bioRxiv2025

Targeting the translation machinery: The RNase Y specificity factor Y-complex coordinates ribosome degradation

Limiting the synthesis and activity of ribosomes is crucial for adaptation to stresses, such as heat or nutrient starvation. In Bacillus subtilis, this can be achieved through the coordinated action of the alarmones (p)ppGpp and the transcription factor Spx. Here, we performed a genetic screen to uncover novel factors contributing to the heat shock response of B. subtilis. We identified the Y-complex, which confers specificity to the endonuclease RNase Y, as a critical player during stress conditions, such as heat or transition into stationary phase. This protein complex is required for processing diverse RNAs, notably the maturation of mRNAs encoding proteins involved in translation and metabolism. We further demonstrate that the Y-complex and RNase Y initiate the degradation of rRNAs of mature ribosomes, lowering their abundance. We propose that the Y-complex is a regulatory hub that modulates gene expression, adjusts protein synthesis and resource allocation.

microbiology↗

bioRxiv2024

Novel RNA-binding protein YebC enhances translation of proline-rich amino acid stretches in bacteria

The ribosome employs a set of highly conserved translation factors to efficiently synthesise proteins. Some translation factors interact with the ribosome in a transient manner and are thus challenging to identify. However, proteins involved in translation can be specifically identified by their interaction with ribosomal RNAs. Using a combination of proteomics approaches, we identified novel RNA binding proteins in the pathogenic bacterium Streptococcus pyogenes. One of these, a universally conserved protein YebC, was shown to transiently interact with 23S rRNA near the peptidyl-transferase centre. Deletion of yebC moderately affected the physiology and virulence of S. pyogenes. We performed ribosome profiling and detected increased pausing at proline-rich amino acid stretches in the absence of functional YebC. Further results obtained with in vivo reporters and in vitro translation system suggest that YebC is a novel translation factor required for efficient translation of proteins with proline-rich motifs.

molecular biology↗

bioRxiv2019

Structural and mutational analysis of the ribosome-arresting human XBP1u

XBP1u, a central component of the unfolded protein response (UPR), is a mammalian protein containing a functionally critical translational arrest peptide (AP). Here, we present a 3 [A] cryo-EM structure of the stalled human XBP1u AP. It forms a unique turn in the upper part of the ribosomal exit tunnel and causes a subtle distortion of the peptidyl transferase center, explaining the temporary translational arrest induced by XBP1u. During ribosomal pausing the hydrophobic region 2 (HR2) of XBP1u is recognized by SRP, but fails to efficiently gate the Sec61 translocon. An exhaustive mutagenesis scan of the XBP1u AP revealed that only 10 out of 21 mutagenized positions in the XBP1u AP are optimal with respect to translational arrest activity. Thus, XBP1u has evolved to induce an intermediate level of translational arrest, allowing efficient targeting by SRP without activating the Sec61 channel and thereby serving its central function in the UPR.

biochemistry↗