The Polyadenylation Complex

An auxiliary downstream factor, DSEF-1 (Down Stream Element Factor-1), assists in the assembly of the core polyadenylation complex on to the 3' end of the pre-messenger RNA.  A model representation.

Cleavage-Polyadenylation, a posttranscriptional event of mammalian gene expression, requires a complex assembly of several protein factors on to the 3' end of pre-messenger RNAs (See Reviews). Formation of  the Cleavage-Polyadenylation Complex is directed by conserved sequence elements present upstream and downstream of the actual Cleavage-Polyadenylation site (PA Site) on the RNA substrate.

The Core Cleavage-Polyadenylation Complex

DSEF-1 is the First Auxiliary Downstream Factor

Review References

The Core Cleavage-Polyadenylation Complex Consists of the following:

• Four sub-units of CPSF (Cleavage and Polyadenylation Specificity Factor), that recognizes the highly conserved upstream AAUAAA element in the 3' end of mammalian pre-mRNAs.

• Three sub-units of CstF (Cleavage Stimulation Factor), that recognizes the downstrean  U-rich element in the 3' end of mammalian pre-mRNAs. CstF assembly on the RNA substrate requires its concomitant association with CPSF.

• Two multi sub-unit Cleavage Factors (CF I and CF II), that carry out the endonucleolytic cleavage of the RNA substrate.

• A PAP (Poly A Polymerase) which is also required for cleavage of most pre-mRNAs.

See Reviews for more details

DSEF-1 is the First Auxiliary Downstream Factor:

• We have identified the first auxiliary downstream element which is a G-rich Sequence (GRS) and is located 3' of the core U-rich element of SV40 late polyadenylation signal (Bagga et. al., 1995).

• We have also purified and cloned an auxiliary factor, DSEF-1 (Down Stream Element Factor-1), that selectively interacts with GRS and stimulates the efficiency of 3' end processing ( Bagga et. al,. 1995; Bagga et. al., 1998).

• Our observations strongly suggest that DSEF-1 assists and stabilizes the assembly of core Cleavage-Polyadenylation complex on to the pre-mRNA substrate (Bagga et. al., 1998).

• Studies also suggest an interaction between  DSEF-1 and CstF  to be responsible for the stabilization effect ( Bagga et. al,. 1997; Bagga et. al., 1998).

Selected Reviews:

• Soller, M. (2006) Pre-messenger RNA processing and its regulation: a genomic perspective. Cell Mol Life Sci. 63, 796-819.

• Gilmartin, G. M. (2005) Eukaryotic mRNA 3' processing: a common means to different ends. Genes Dev. 19, 2517-2521.

• Shatkin AJ and Manley JL. (2000) The ends of the affair: capping and polyadenylation. Nat Struct Biol.  7(10):838-842.

• Proudfoot N.(2000) Connecting transcription to messenger RNA processing. Trends Biochem Sci.  25(6):290-293.

• Minvielle-Sebastia L and Keller W.(1999) mRNA polyadenylation and its coupling to other RNA processing reactions and to transcription.Curr Opin Cell Biol  11(3):352-357.

• Wahle E and Ruegsegger U.(1999) 3'-End processing of pre-mRNA in eukaryotes. FEMS Microbiol Rev.  23(3):277-295.

• Zhao J, Hyman L and Moore C.(1999) Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.Microbiol Mol Biol Rev   63(2):405-445.

• Colgan DF and Manley JL.(1997) Mechanism and regulation of mRNA polyadenylation. Genes Dev.  11(21):2755-2766.

• Edwalds-Gilbert G, Veraldi KL and Milcarek C.(1997) Nucleic Acid Research.  25(13):2547-2561.

• Wahle, E.  and Kuhn, U. (1997) The mechanism of 3' cleavage and polyadenylation of eukaryotic pre-mRNA.  Progress in Nucleic Acid Research & Molecular Biology.  57:41-71.

• Colgan ,D.F. and Manley J.L. (1997)  Mechanism and regulation of mRNA polyadenylation.  Genes & Development.  11:2755-2766.

• Proudfoot, N. (1996) Ending the message is not so simple. Cell.87: 779-781.

• Wahle, E. and Keller, W. (1996) The biochemistry of polyadenylation. TIBS 21: 247-251.

• Manley, J.L. (1995) A complex protein assembly catalyzes polyadenylation of mRNA precursors. Curr Opin Genet Dev. 5:222-228.

• Keller, W. (1995) No end yet to messenger RNA 3' processing! Cell. 81: 829-832.