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Cleavage and polyadenylation is an essential processing reaction required for the maturation of pre-mRNAs into stable, export- and translation-competent mature mRNA molecules. This reaction requires the assembly of a multimeric protein complex onto a bipartite core sequence element consisting of an AAUAAA hexamer and a GU/U-rich downstream sequence element. In this study we have analyzed 3' end processing of the human melanocortin 1 receptor gene (MC1R). The MC1R gene is an intron-free transcription unit, and its poly(A) site lacks a defined U/GU-rich element. We describe two G-rich sequence elements that are critical for efficient cleavage at the MC1R poly(A) site. The first element is located 30 nucleotides downstream of the cleavage site and acts as an essential closely positioned enhancer. The second G-rich region is positioned more than 440 nucleotides downstream of the MC1R processing site and is instrumental for optimal processing efficiency. Both G-rich sequences contain clusters of heterogeneous nuclear ribonucleoprotein binding motifs and act together to enhance cleavage at the MC1R poly(A) site.

Original publication

DOI

10.1128/MCB.01821-06

Type

Journal article

Journal

Mol Cell Biol

Publication Date

03/2007

Volume

27

Pages

1568 - 1580

Keywords

3' Untranslated Regions, Base Sequence, Cell Line, Transformed, Cell Line, Tumor, Enhancer Elements, Genetic, Genes, Regulator, Genes, Reporter, HeLa Cells, Humans, Melanoma, Poly A, RNA Precursors, RNA Processing, Post-Transcriptional, Receptor, Melanocortin, Type 1, Regulatory Sequences, Nucleic Acid