Abstract

Computational and experimental evidence is given for alternative splicing at the unusual GYNGYN motif in several species, enabling in most cases subtle protein variations.

Highlights

  • Splice donor sites have a highly conserved GT or GC dinucleotide and an extended intronic consensus sequence GTRAGT that reflects the sequence complementarity to the U1 snRNA

  • Investigating what distinguishes alternatively from not alternatively spliced GYNGYN donors, we found differences in the binding to U1 snRNA, a strong correlation between U1 snRNA binding strength and the preferred donor, over-represented sequence motifs in the adjacent introns, and a higher conservation of the exonic and intronic flanks between human and mouse

  • Alternative splicing at tandem donor sites the great majority of introns begins with a GT dinucleotide, a small fraction of 0.76% begins with GC [1]

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Summary

Introduction

Splice donor sites have a highly conserved GT or GC dinucleotide and an extended intronic consensus sequence GTRAGT that reflects the sequence complementarity to the U1 snRNA. In the NAGNAG motif (N stands for A, C, G or T/U; throughout the paper we write T instead of U when referring to an RNA sequence), we have termed the upstream acceptor the E acceptor (since the downstream NAG becomes exonic in case of splicing at this site) and the downstream one the I acceptor (since the whole tandem becomes intronic) This splice acceptor motif frequently allows the selection of one of the two AGs in the splice process, resulting in the insertion/deletion (indel) of the I acceptor NAG in mRNAs, preferably if both Ns are either A, C, or T [13,14,15]. These subtle protein changes can result in functional differences for the respective protein isoforms [15,16,17,18]

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