Translation coupled mRNA-decay is a function of both structural and codon level characteristics

Abstract The majority of mRNA degradation occurs co-translationally. Several works in the past elucidated the role of codon composition in regulating co-translational mRNA decay. Integration of mRNA sequence, structure and ribosomal density unravels common regulatory factors of translational and degradation and helps in understanding the intricate association between these two important processes. Co-translational degradation is a two-step process, involving translational stalling and mRNA release for degradation. Our findings highlight the role of Codon Adaptation Index, a sequence-level feature that serves as the primary determinant of translation rates facilitating transcript release from translational machinery upon stalling. Concurrently, cellular endonucleases targeting Internal Unstructured Segments, facilitating easy degradation of the stalled mRNA transcripts, influencing their half-lives across the genome and over evolutionary timescales.