Cleavage of mRNA at the 3'-end

Stable Identifier
R-HSA-72180
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Endonucleolytic cleavage separates the pre-mRNA into an upstream fragment destined to become the mature mRNA, and a downstream fragment that is rapidly degraded. Cleavage depends on two signals in the RNA, a highly conserved hexanucleotide, AAUAAA, 10 to 30 nucleotides upstream of the cleavage site, and a poorly conserved GU- or U-rich downstream element. Additional sequences, often upstream of AAUAAA, can enhance the efficiency of the reaction. Cleavage occurs most often after a CA dinucleotide. A single gene can have more than one 3' processing site.

Cleavage is preceded by the assembly of a large processing complex, the composition of which is poorly defined. ATP, but not its hydrolysis, is required for assembly. Cleavage at the 3'-end of mRNAs depends on a number of protein factors. CPSF, a heterotetramer, binds specifically to the AAUAAA sequence. The heterotrimer CstF binds the downstream element. CF I, which appears to be composed of two subunits, one of several related larger polypeptides and a common smaller one, also binds RNA, but with unknown specificity. RNA recognition by these proteins is cooperative. Cleavage also requires CF II, composed of at least two subunits, and poly(A) polymerase, the enzyme synthesizing the poly(A) tail in the second step of the reaction. The polypeptide catalyzing the hydrolysis of the phosphodiester bond remains to be identified.

Cleavage produces a 3'-OH on the upstream fragment and a 5'-phosphate on the downstream fragment. At some unknown point after cleavage, the downstream RNA fragment, CstF, CF I and CF II are thought to be released, whereas CPSF and poly(A) polymerase remain to carry out polyadenylation.

Literature References
PubMed ID Title Journal Year
10357856 Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.

Zhao, J, Hyman, L, Moore, C

Microbiol Mol Biol Rev 1999
10371034 3'-End processing of pre-mRNA in eukaryotes.

Wahle, E, Rüegsegger, U

FEMS Microbiol Rev 1999
Participants
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Event Information
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Catalyst Activity
Catalyst Activity
Title
endonuclease activity of mRNA 3'-end cleavage factor [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Created
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