In: Anatomy and Physiology
Why can’t the 3’ end of pre-mRNA be modified at the same time as the 5’ cap is place on the other end?
The pre-mRNA synthesized in the nucleus has to be transported into the cytoplasm in eukaryotes. Pre-mRNA undergoes post-transcriptional processing and forms mature mRNA which then enters the cytoplasm for translation. Post-transcriptional processing includes 5’ capping, 3’ polyadenylation and alternative splicing of introns.
Very early during transcription by RNA pol II, a 5’ m7G Cap is added to 5’ end of the mRNA. mRNA transcription occurs in 5’ to 3’ direction. The 5’ cap is added when the pre-mRNA is 20 nucleotides long. This cap is required for protein translation as it is recognize by eukaryotic translation initiation factor eIF-4E. However, it has functions even before translation. It is required for alternative splicing of introns, and also essential for processing the 3’ end of the pre-mRNA. It also helps in export of mature mRNA to the cytoplasm. It protects the mRNA from actions of 5’ to 3’ exonucleases.
The 3’ poly A tails is added only after complete pre-mRNA is formed. It protects the mRNA from degradation and allows its stable translocation to cytoplasm. Histone pre-mRNA lack poly A tail. Poly A tail helps in protein translation.
Thus, 5’ Cap and 3’ poly A tail are added at different times on pre-mRNA formation. The 5’ Cap is required for processing of 3’ end of the pre-mRNA. The cap binding complex CBC, which binds to the cap, is required for the endonucleolytic cleavage step of polyadenylation. Thus, polyadenylation cannot occur if the 5’ capping has not occurred previously. Cap also is involved in termination of transcription and exosomal degradation. If capping has not occurred, then the polyadenylation will also fail. 5’ Capping has important role in transcription and post transcriptional processing of mRNA while 3’ poly A tail mostly have role in post-transcriptional processing. This is the reason 5’ capping occurs much prior to 3’ poly A tail addition, in eukaryotes. 5' Cap should already be added before poly A tail can be added at 3' end.