Abstract
A majority of messenger RNA precursors (pre-mRNAs) in the higher eukaryotes undergo alternative splicing to generate more than one mature product. By targeting the open reading frame region this process increases diversity of protein isoforms beyond the nominal coding capacity of the genome. However, alternative splicing also frequently controls output levels and spatiotemporal features of cellular and organismal gene expression programs. Here we discuss how these non-coding functions of alternative splicing contribute to development through regulation of mRNA stability, translational efficiency and cellular localization.
Highlights
Eukaryotic genomes contain a large number of intronic sequences that “split” gene-encoded messages at the level of DNA and mRNA precursor transcripts but are spliced out from the mature mRNAs [1]
Blurring the classical division of mRNA into protein-coding and regulatory noncoding sequences, recent studies suggest that alternative splicing (AS) can expose or mask cis-regulation elements in the open reading frame (ORF) region as well as in the 5 and 3 untranslated regions (UTRs)
The widespread occurrence of such “non-coding” functions of AS across eukaryotic domain and their occasional association with ultraconserved sequences argue that there is a strong evolutionary pressure to maintain this form of regulation
Summary
Eukaryotic genomes contain a large number of intronic sequences that “split” gene-encoded messages at the level of DNA and mRNA precursor transcripts (pre-mRNAs) but are spliced out from the mature mRNAs [1]. ∼21,000 human genes are estimated to give rise to ∼80,000 differentially spliced mRNA species [15] that often encode distinct protein isoforms Such AS-mediated expansion of proteome complexity might have facilitated progressive evolution of multicellular eukaryotes [16,17]. A large fraction of AS events occurs in the 5 and 3 untranslated regions (UTRs) of mRNA flanking the open reading frame (ORF). This has no effect on the polypeptide sequence but instead may modulate other aspects of mRNA behavior.
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