Cleavage and polyadenylation specificity factor (CPSF) is involved in the
cleavage of the
3' signaling region from a newly synthesized pre-
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the p ...
(pre-mRNA) molecule in the process of
gene transcription
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...
. It is the first protein to bind to the signaling region near the cleavage site of the pre-mRNA, to which the
poly(A) tail
Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In euk ...
will be added by
polynucleotide adenylyltransferase
In enzymology, a polynucleotide adenylyltransferase () is an enzyme that catalyzes the chemical reaction
:ATP + RNA-3'OH \rightleftharpoons pyrophosphate + RNApA-3'OH
Thus, the two substrates of this enzyme are ATP and RNA, whereas its two p ...
. The upstream signaling region has the canonical
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
sequence AAUAAA, which is highly conserved across the vast majority of pre-mRNAs. A second downstream signaling region, located on the portion of the pre-mRNA that is cleaved before polyadenylation, consists of a GU-rich region required for efficient processing.
Structure
CPSF is a
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein c ...
, consisting of four proteins:
CPSF-73
Cleavage and polyadenylation specificity factor subunit 3 is a protein that in humans is encoded by the ''CPSF3'' gene.
Model organisms
Model organisms have been used in the study of CPSF3 function. A conditional knockout mouse line called ''Cp ...
,
CPSF-100
Cleavage and polyadenylation specificity factor subunit 2 is a protein that in humans is encoded by the ''CPSF2'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of hered ...
,
CPSF-30
Cleavage and polyadenylation specificity factor subunit 4 is a protein that in humans is encoded by the ''CPSF4'' gene.
Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the influenza A virus NS1 protein requires its effector ...
and
CPSF-160
Cleavage and polyadenylation specificity factor subunit 1 is a protein that in humans is encoded by the ''CPSF1'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of hered ...
.
CPSF-73 is a zinc-dependent
hydrolase
Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...
which cleaves the mRNA precursor just downstream the polyadenylation signal sequence AAUAAA.
CPSF-160 is the largest subunit of CPSF and directly binds to the AAUAAA polyadenylation signal.
CPSF recruits proteins to the 3' region. Identified proteins that are coordinated by CPSF activity include:
cleavage stimulatory factor Cleavage stimulatory factor or cleavage stimulation factor (CstF or CStF) is a heterotrimeric protein, made up of the proteins CSTF1 (55kDa), CSTF2 (64kDa) and CSTF3 (77kDa), totalling about 200 kDa. It is involved in the cleavage of the 3' signali ...
and the two poorly understood
cleavage factor __NOTOC__
Cleavage factors are two closely associated protein complexes involved in the cleavage of the 3' untranslated region of a newly synthesized pre-messenger RNA (mRNA) molecule in the process of gene transcription. The cleavage is the first ...
s. The binding of the
polynucleotide adenylyltransferase
In enzymology, a polynucleotide adenylyltransferase () is an enzyme that catalyzes the chemical reaction
:ATP + RNA-3'OH \rightleftharpoons pyrophosphate + RNApA-3'OH
Thus, the two substrates of this enzyme are ATP and RNA, whereas its two p ...
responsible for actually synthesizing the tail is a necessary prerequisite for cleavage, thus ensuring that cleavage and polyadenylation are tightly coupled processes.
Genes
* ''
CPSF1
Cleavage and polyadenylation specificity factor subunit 1 is a protein that in humans is encoded by the ''CPSF1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredi ...
'', ''
CPSF2
Cleavage and polyadenylation specificity factor subunit 2 is a protein that in humans is encoded by the ''CPSF2'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredi ...
'', ''
CPSF3
Cleavage and polyadenylation specificity factor subunit 3 is a protein that in humans is encoded by the ''CPSF3'' gene.
Model organisms
Model organisms have been used in the study of CPSF3 function. A conditional knockout mouse line called ''Cps ...
'', ''
CPSF4
Cleavage and polyadenylation specificity factor subunit 4 is a protein that in humans is encoded by the ''CPSF4'' gene.
Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the influenza A virus NS1 protein requires its effector ...
'', ''
CPSF6''
References
* Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. (2004). ''Molecular Cell Biology.'' WH Freeman: New York, NY. 5th ed.
*
External links
*
Protein complexes
Gene expression
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