Understanding the molecular mechanism linking mRNA decay and capping with post-transcriptional gene silencing

Genetic information of eukaryotic genes is decoded through formation of mRNA in the nucleus (transcription) that is then used as a template to produce protein in the cytoplasm (translation). During this gene expression process, transcribed mRNAs are capped, spliced, polyadenylated, and then transported to the cytoplasm to direct protein synthesis. Cells use highly regulated processes to control mRNA quality to ensure the integrity of protein-encoding gene expression. The mRNA quality control process includes degradation of aberrant and unneeded mRNAs. mRNA decay generally uses exoribonucleases to degrade mRNAs from both ends after removal of the 5′ m7G cap and the 3′ poly(A) tail. Defects in the RNA decay pathway can lead to accumulation of aberrant mRNAs, which could be used by RNA-dependent RNA polymerase (RDR) to produce double-stranded RNAs (dsRNAs). dsRNAs are then processed by DICER-LIKE proteins to form short interfering RNAs (siRNAs). siRNAs inactivate target mRNAs in a process termed post-transcriptional gene silencing (PTGS).