What is Polyadenylation?
In most of the eukaryotes, mRNAs in the cells undergoes many complications to modify and get processed before undergoing the process of translation.
These modification process involves some chemical modifications, polyadenylation and removal of introns.
Here we will be discussing briefly about polyadenylation. Polyadenylation is a process of adding a poly(A) tail to the mRNAs, as these polyadenyl tails consists of numerous adenine monophosphates.
It is an important process in all the eukaryotes to produce a mature messenger RNA which is greatly used for transcribing. So, it forms a larger part of the gene expression process.
Poly (A) tail is very much important for the nuclear export, translation and in maintaining the stability of the mRNA.
This tail is shortened over time, and when it is shortened enough, mRNA is enzymatically degraded,
Features of Polyadenylation
Polyadenylation is a process of addition of poly(A) tail to transcript RNA, typically a messenger RNA (mRNA).
The poly (A) tail contains multiple of adenosine monophosphate, in other terms it can also be said that it is a stretch of RNA which contains only adenine bases.
In eukaryotic organisms’ polyadenylation is considered as a part of process which produces mature messenger RNA for the process of translation.
In many of the bacteria’s the poly(a) tail promotes degradation in the mRNA. Which therefore forms a part of the large processor in the gene expression.
The poly (A) tail is very much important for the nuclear export, translation and in maintain the stability of mRNA.
The tail is shortened upon time until it becomes short enough when the mRNA is enzymatically degraded. However, in some cell types mRNAs has a short poly(A) tails which are stored for the activation at the later times with the help of re-polyadenylation in the cytosol.
Where as in bacteria the polyadenylation promotes the degradation of RNA; in certain cases, this condition leads to non-coding of eukaryotic RNAs.
RNA and Polyadenylation
RNA is one of the large biomolecules, where each of them plays an important role in building the nucleotides by acting as a building block.
The term poly (A) denotes polyadenylic acid tail which reflects the RNA nucleotides for a base Adenine denoted by a letter A, and the other bases where G is noted for Guanine and C is noted for cytosine and U is noted as Uracil.
RNA is produced from the DNA during the transcribing process. During this conversion RNA sequences are written in a direction of 5’ to 3’ end.
Where 5’ end is the part of an RNA molecule which is transcribed first and later the 3’ end is transcribed.
The 3’end is the place where polyadenyle tail is found on the polyadenylated RNAs.
Messenger RNA is a kind of RNA which has a coding region and acts as a template for the synthesis of proteins which is otherwise called as translation.
Whereas the rest of the parts expect coding regions in the messenger RNAs remain as the untranslated regions and they just tunes how active the mRNA is.
This condition can be found in so many RNAs which are not being translated. And they are commonly called as non-coding RNAs.
Similar to that of the untranslated regions, many of the non-coding RNAs also performs some regulatory roles.
The mRNA molecules which is present in both prokaryotes and eukaryotes have the polyadenylated 3’ends, along with the prokaryotic poly (A) tails are generally shorter and less mRNA molecules polyadenylated.
Mechanism of Polyadenylation
Polyadenylation process initiates in the nucleus of the eukaryotes which works in the RNA polymerase II, as a precursor mRNA, Where the 3’ part of the newly produced RNA and the polyadenylates are resultant of this cleavage process.
This process of cleavage is being catalyzed by the enzyme CPSF and it occurs 10-30 nucleotides downstream of its binding site.
This site mostly consists of a polyadenylation signal sequence AAUAA in the RNA, but the variants of it binds weaklier to the CPSF.
Further two other proteins are added specifically to the binding site of RNA; which are named as CstF and CFI, where the CstF binds to the GU region then downstream of the CPSFs site.
CFI recognizes at the third site on the RNA in a UGUAA sequence present in the mammals and recruits the CPSF IF THE AAUAA sequence is missing.
The polyadenylation signals sequence motif is recognized by the RNA cleavage complex which varies between the each of the eukaryotes.
Mostly the human polyadenylation sites contain the AAUAA sequence, but this sequence is less common in fungi and in plants.
RNA is cleaved before transcription termination because, CstF binds to the RNA polymerase II because the poorly understood mechanism which signals for the RNA polymerase II slip off out of the transcript.
Cleavage involves the protein CSF II though it is unknown how, the cleavage sites are associated with a polyadenylation signal it varies up to an average of 50 nucleotides.
During the cleaving of RNA, polyadenylation usually starts and it is catalyzed by the enzyme polyadenylate polymerase which builds the poly(A) tail which adds adenosine monophosphate units from the adenosine triphosphate to the RNA which cleaves off phosphate.
Another protein, PAB2 binds with the newly formed short poly (A) tail and it also increases the affinity of polyadenylate polymerase for the RNA.
When the poly(A) tail reaches an approximate of 250 nucleotides long it cannot bind with the CPSF and thus the polyadenylation stops determining the length of the poly(A) tail.
CPSF is in contact with the RNA polymerase II thus allowing it to rise a signal to the polymerase to end the process of transcription.
When the RNA polymerase II reaches a termination sequence, the transcription comes to an end with an signaling.
The polyadenylation mechanism is sometimes linked to the spliceosome physically which removes the introns from the RNAs.
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- Alternative cleavage and polyadenylation: extent, regulation and function. Nat Rev Genet . 2013 Jul;14(7):496-506.
- Implications of polyadenylation in health and disease. Nucleus . 2014;5(6):508-19.