Cleavage factor

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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 step in adding a polyadenine tail to the pre-mRNA, which is one of the necessary post-transcriptional modifications necessary for producing a mature mRNA molecule.

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In mammals, the two cleavage factors are known as CFIm and CFIIm. The proteins that constitute these complexes are recruited to the cleavage site by cleavage and polyadenylation specificity factor and cleavage stimulatory factor, and form a larger complex that also includes polyadenine polymerase, which performs the polyadenylation reaction.

The CFIm complex

Involved in the earliest step for the formation of the active cleavage complex, the CFIm complex is formed by three proteins of 25, 59 and 68 kDa, respectively: [1]

CFIm25 and CFIm68 are sufficient for the activity of the complex, proving the expected redundancy of CFIm68 and CFIm59, which share great sequence similarity. [1]

The CFIIm complex

The CFIIm complex is responsible for transcription termination and triggering the disassembly of the elongation complex. It is composed of only two proteins: [2]

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<span class="mw-page-title-main">Messenger RNA</span> RNA that is read by the ribosome to produce a protein

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.

In genetics, a transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription. This sequence mediates transcriptional termination by providing signals in the newly synthesized transcript RNA that trigger processes which release the transcript RNA from the transcriptional complex. These processes include the direct interaction of the mRNA secondary structure with the complex and/or the indirect activities of recruited termination factors. Release of the transcriptional complex frees RNA polymerase and related transcriptional machinery to begin transcription of new mRNAs.

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 eukaryotes, polyadenylation is part of the process that produces mature mRNA for translation. In many bacteria, the poly(A) tail promotes degradation of the mRNA. It, therefore, forms part of the larger process of gene expression.

<span class="mw-page-title-main">Primary transcript</span> RNA produced by transcription

A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs are modified in preparation for translation. For example, a precursor mRNA (pre-mRNA) is a type of primary transcript that becomes a messenger RNA (mRNA) after processing.

In molecular biology, a termination factor is a protein that mediates the termination of RNA transcription by recognizing a transcription terminator and causing the release of the newly made mRNA. This is part of the process that regulates the transcription of RNA to preserve gene expression integrity and are present in both eukaryotes and prokaryotes, although the process in bacteria is more widely understood. The most extensively studied and detailed transcriptional termination factor is the Rho (ρ) protein of E. coli.

<span class="mw-page-title-main">Post-transcriptional modification</span> RNA processing within a biological cell

Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, functional RNA molecule that can then leave the nucleus and perform any of a variety of different functions in the cell. There are many types of post-transcriptional modifications achieved through a diverse class of molecular mechanisms.

Cleavage stimulatory factor or cleavage stimulation factor 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' signaling region from a newly synthesized pre-messenger RNA (mRNA) molecule. CstF is recruited by cleavage and polyadenylation specificity factor (CPSF) and assembles into a protein complex on the 3' end to promote the synthesis of a functional polyadenine tail, which results in a mature mRNA molecule ready to be exported from the cell nucleus to the cytosol for translation.

Cleavage and polyadenylation specificity factor (CPSF) is involved in the cleavage of the 3' signaling region from a newly synthesized pre-messenger RNA (pre-mRNA) molecule in the process of gene transcription. 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 will be added by polynucleotide adenylyltransferase. The upstream signaling region has the canonical nucleotide 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.

<span class="mw-page-title-main">Long terminal repeat</span>

A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or a retroviral provirus. All retroviral genomes are flanked by LTRs, while there are some retrotransposons without LTRs. Typically, an element flanked by a pair of LTRs will encode a reverse transcriptase and an integrase, allowing the element to be copied and inserted at a different location of the genome. Copies of such an LTR-flanked element can often be found hundreds or thousands of times in a genome. LTR retrotransposons comprise about 8% of the human genome.

<span class="mw-page-title-main">Polynucleotide adenylyltransferase</span>

In enzymology, a polynucleotide adenylyltransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">CSTF2</span> Protein-coding gene in the species Homo sapiens

Cleavage stimulation factor 64 kDa subunit is a protein that in humans is encoded by the CSTF2 gene.

<span class="mw-page-title-main">NUDT21</span> Protein-coding gene in the species Homo sapiens

Cleavage and polyadenylation specificity factor subunit 5 (CPSF5) is an enzyme that in humans is encoded by the NUDT21 gene. It belongs to the Nudix family of hydrolases.

<span class="mw-page-title-main">CPSF2</span> Protein-coding gene in the species Homo sapiens

Cleavage and polyadenylation specificity factor subunit 2 is a protein that in humans is encoded by the CPSF2 gene. This protein is a subunit of the cleavage and polyadenylation specificity factor (CPSF) complex which plays a key role in pre-mRNA 3' end processing and polyadenylation.

<span class="mw-page-title-main">CPSF1</span> Protein-coding gene in the species Homo sapiens

Cleavage and polyadenylation specificity factor subunit 1 is a protein that in humans is encoded by the CPSF1 gene.

<span class="mw-page-title-main">PAPOLA</span> Protein-coding gene in the species Homo sapiens

Poly(A) polymerase alpha is an enzyme that in humans is encoded by the PAPOLA gene.

<span class="mw-page-title-main">CPSF3</span> Protein-coding gene in the species Homo sapiens

Cleavage and polyadenylation specificity factor subunit 3 is a protein that in humans is encoded by the CPSF3 gene.

<span class="mw-page-title-main">CPSF4</span> Protein-coding gene in the species Homo sapiens

Cleavage and polyadenylation specificity factor subunit 4 is a protein that in humans is encoded by the CPSF4 gene.

<span class="mw-page-title-main">CPSF6</span> Protein-coding gene in the species Homo sapiens

Cleavage and polyadenylation specificity factor subunit 6 is a protein that in humans is encoded by the CPSF6 gene.

<span class="mw-page-title-main">CPSF7</span> Protein-coding gene in the species Homo sapiens

Cleavage and polyadenylation specificity factor subunit 7 is a protein that in humans is encoded by the CPSF7 gene.

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

References

  1. 1 2 Hardy, J. G.; Norbury, C. J. (15 August 2016). "Cleavage factor Im (CFIm) as a regulator of alternative polyadenylation". Biochemical Society Transactions. 44 (4): 1051–1057. doi: 10.1042/BST20160078 . PMID   27528751.
  2. Ustyantsev, I. G.; Golubchikova, J. S.; Borodulina, O. R.; Kramerov, D. A. (9 May 2017). "Canonical and noncanonical RNA polyadenylation". Molecular Biology. 51 (2): 226–236. doi:10.1134/S0026893317010186. PMID   28537233. S2CID   34817705.

Further reading