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Mechanism of u1a pre-mrna polyadenylation inhibition by u1a protein


The human U1 small nuclear ribonucleoprotein (snRNP) is one of a family snRNPs that play an essential role in the removal of introns from pre-messenger RNA (pre-mRNA). The U1 snRNP-specific U1A protein autoregulates its production by binding to its own pre-mRNA and inhibiting polyadenylation. Two molecules of U1A were shown to bind to a conserved region in the 3' untranslated region of U1A pre-mRNA to produce efficient inhibition of polyadenylation. The mechanism of this regulation has been elucidated in vitro: U1A protein bound to its own pre-mRNA inhibits polyadenylation activity of poly(A) polymerase (PAP) by a direct and specific interaction between U1A and PAP.
The tripartite complex between U1A pre-mRNA, U1A protein and PAP and th relationship between its structure and function in inhibition of polyadenylation i71 vitro will be investigated. I will then experiment the possibility that the U1APAP interaction used in autoregulation of U1A protein synthesis might also be involved in either the other example of U1A regulation of polyadenylation (of SV40 late mRNA) or in the coupling of splicing and polyadenylation that has been shown to exist.

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