Transcripts with codons that trigger the P-site tRNA–mediated mRNA decay are enriched with optimal codons DOI Creative Commons
Rodolfo L. Carneiro, Fernando L. Palhano

Published: April 16, 2025

Abstract Synonymous codon usage is a major determinant of mRNA half-life in yeast, functioning as second layer genetic information during translation. In this system, the CCR4-NOT complex plays key role by interacting with ribosome when both its A and E sites are vacant—a state that typically occurs non-optimal codon, i.e., one low tRNA availability, occupies site. The then recruits decay machinery, leading to shorter half-lives for transcripts enriched codons. humans, extent which affects stability remains unclear. Recent studies have shown recruitment humans shares some similarities yeast but also exhibits significant mechanistic differences. particular, binding depends on presence specific arginine codons —CGG, CGA, or AGG—at P site ribosome, process termed P-site tRNA-mediated (PTMD). PTMD requires slow decoding at site, enabling E-site vacancy subsequent CNOT3. Using high-throughput analyses public datasets, we investigated how human differ from rest transcriptome terms optimality, half-life, protein abundance. We find PTMD-target predominantly present overall optimal longer half-lives. This suggests that, contrast preferentially shortens otherwise stable transcripts, rather than contributing degradation inherently unstable ones.

Language: Английский

Transcripts with codons that trigger the P-site tRNA–mediated mRNA decay are enriched with optimal codons DOI Creative Commons
Rodolfo L. Carneiro, Fernando L. Palhano

Published: April 16, 2025

Abstract Synonymous codon usage is a major determinant of mRNA half-life in yeast, functioning as second layer genetic information during translation. In this system, the CCR4-NOT complex plays key role by interacting with ribosome when both its A and E sites are vacant—a state that typically occurs non-optimal codon, i.e., one low tRNA availability, occupies site. The then recruits decay machinery, leading to shorter half-lives for transcripts enriched codons. humans, extent which affects stability remains unclear. Recent studies have shown recruitment humans shares some similarities yeast but also exhibits significant mechanistic differences. particular, binding depends on presence specific arginine codons —CGG, CGA, or AGG—at P site ribosome, process termed P-site tRNA-mediated (PTMD). PTMD requires slow decoding at site, enabling E-site vacancy subsequent CNOT3. Using high-throughput analyses public datasets, we investigated how human differ from rest transcriptome terms optimality, half-life, protein abundance. We find PTMD-target predominantly present overall optimal longer half-lives. This suggests that, contrast preferentially shortens otherwise stable transcripts, rather than contributing degradation inherently unstable ones.

Language: Английский

Citations

0