Polyadenylation

Polyadenylation is the addition of a poly(A) tail to a messenger RNA. The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA (mRNA) for translation. It, therefore, forms part of the larger process of gene expression.CPSF: cleavage/polyadenylation specificity factorCstF: cleavage stimulation factorPAP: polyadenylate polymerasePABII: polyadenylate binding protein 2CFI: cleavage factor ICFII: cleavage factor II Polyadenylation is the addition of a poly(A) tail to a messenger RNA. The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA (mRNA) for translation. It, therefore, forms part of the larger process of gene expression. The process of polyadenylation begins as the transcription of a gene terminates. The 3'-most segment of the newly made pre-mRNA is first cleaved off by a set of proteins; these proteins then synthesize the poly(A) tail at the RNA's 3' end. In some genes these proteins add a poly(A) tail at one of several possible sites. Therefore, polyadenylation can produce more than one transcript from a single gene (alternative polyadenylation), similar to alternative splicing. The poly(A) tail is important for the nuclear export, translation, and stability of mRNA. The tail is shortened over time, and, when it is short enough, the mRNA is enzymatically degraded. However, in a few cell types, mRNAs with short poly(A) tails are stored for later activation by re-polyadenylation in the cytosol. In contrast, when polyadenylation occurs in bacteria, it promotes RNA degradation. This is also sometimes the case for eukaryotic non-coding RNAs. mRNA molecules in both prokaryotes and eukaryotes have polyadenylated 3'-ends, with the prokaryotic poly(A) tails generally shorter and less mRNA molecules polyadenylated. RNAs are a type of large biological molecules, whose individual building blocks are called nucleotides. The name poly(A) tail (for polyadenylic acid tail) reflects the way RNA nucleotides are abbreviated, with a letter for the base the nucleotide contains (A for adenine, C for cytosine, G for guanine and U for uracil). RNAs are produced (transcribed) from a DNA template. By convention, RNA sequences are written in a 5' to 3' direction. The 5' end is the part of the RNA molecule that is transcribed first, and the 3' end is transcribed last. The 3' end is also where the poly(A) tail is found on polyadenylated RNAs. Messenger RNA (mRNA) is RNA that has a coding region that acts as a template for protein synthesis (translation). The rest of the mRNA, the untranslated regions, tune how active the mRNA is. There are also many RNAs that are not translated, called non-coding RNAs. Like the untranslated regions, many of these non-coding RNAs have regulatory roles. In nuclear polyadenylation, a poly(A) tail is added to an RNA at the end of transcription. On mRNAs, the poly(A) tail protects the mRNA molecule from enzymatic degradation in the cytoplasm and aids in transcription termination, export of the mRNA from the nucleus, and translation. Almost all eukaryotic mRNAs are polyadenylated, with the exception of animal replication-dependent histone mRNAs. These are the only mRNAs in eukaryotes that lack a poly(A) tail, ending instead in a stem-loop structure followed by a purine-rich sequence, termed histone downstream element, that directs where the RNA is cut so that the 3' end of the histone mRNA is formed. Many eukaryotic non-coding RNAs are always polyadenylated at the end of transcription. There are small RNAs where the poly(A) tail is seen only in intermediary forms and not in the mature RNA as the ends are removed during processing, the notable ones being microRNAs. But, for many long noncoding RNAs – a seemingly large group of regulatory RNAs that, for example, includes the RNA Xist, which mediates X chromosome inactivation – a poly(A) tail is part of the mature RNA. The processive polyadenylation complex in the nucleus of eukaryotes works on products of RNA polymerase II, such as precursor mRNA. Here, a multi-protein complex (see components on the right) cleaves the 3'-most part of a newly produced RNA and polyadenylates the end produced by this cleavage. The cleavage is catalysed by the enzyme CPSF and occurs 10–30 nucleotides downstream of its binding site. This site often has the polyadenylation signal sequence AAUAAA on the RNA, but variants of it that bind more weakly to CPSF exist. Two other proteins add specificity to the binding to an RNA: CstF and CFI. CstF binds to a GU-rich region further downstream of CPSF's site. CFI recognises a third site on the RNA (a set of UGUAA sequences in mammals) and can recruit CPSF even if the AAUAAA sequence is missing. The polyadenylation signal – the sequence motif recognised by the RNA cleavage complex – varies between groups of eukaryotes. Most human polyadenylation sites contain the AAUAAA sequence, but this sequence is less common in plants and fungi.