Hello Isha Pandey

Various RNA-binding proteins regulate almost every step of an mRNA’s life, from birth (transcription) to death (degradation). A conserved family of RNA-binding proteins, the cytoplasmic poly(A)-binding proteins (PABs) are proteins that cover the poly(A) tails of mRNAs. It is generally assumed that PABs uniformly bind poly(A)-tailed mRNAs.

There are two, poly(A) binding nuclear protein 1 (PABPN1) and cytoplasmic poly(A) binding protein (PABPC) which bind to the poly(A) tail and regulate these processes. PABPN1 stimulates polyadenylation and regulates poly(A) tail length in the nucleus while PABPC facilitates translation and modulates mRNA stability in the cytoplasm.

If non-A nucleotides are used as the tail it would potentially affect PAB binding since the RNA recognition motifs of PABs mainly bind to A-tracts.

However, there have been studies showing the integration of non-A nucleotides (C, G, or U) into the poly(A) tail. For instance, in Hela cells, guanosine was identified as the most abundant non-A nucleotide in the poly(A) tail and exhibited a variable frequency among genes.

Please refer to the references attached below for more information on the incorporation of non-A nucleotides in the tail.

https://pubmed.ncbi.nlm.nih.gov/24582499/

https://pubmed.ncbi.nlm.nih.gov/30026317/

https://pubmed.ncbi.nlm.nih.gov/23748567/

Best.

Thank you so much for answering my question. It did satisfy my curiosity. However, I would like to ask one more question.

So adenine is used to make poly (A) tail because of the presence of poly (A) binding proteins (PABs). But why evolution chose adenine to make this structure ? ( It's the same question like Why did evolution favor ATP and not GTP, TTP or CTP?) I hope my question is not wrong. Thank you again.

Isha Pandey ATP preference might be the molecular fossil taking its origin in earlier prebiotic step of chemical evolution; pls, look, e.g., through this article: Article A prebiotic basis for ATP as the universal energy currency