Abstract
Alternative pre-mRNA splicing provides an effective means for expanding coding capacity of eukaryotic genomes. Recent studies suggest that co-expression of different splice isoforms may increase diversity of RNAs and proteins at a single-cell level. A pertinent question in the field is whether such co-expression is biologically meaningful or, rather, represents insufficiently stringent splicing regulation. Here we argue that isoform co-expression may produce functional outcomes that are difficult and sometimes impossible to achieve using other regulation strategies. Far from being a ‘splicing noise’, co-expression is often established through co-ordinated activity of specific cis-elements and trans-acting factors. Further work in this area may uncover new biological functions of alternative splicing (AS) and generate important insights into mechanisms allowing different cell types to attain their unique molecular identities.
Highlights
Alternative pre-mRNA splicing (AS) allows a single gene to generate more than one mature mRNA species through non-uniform utilization of exonic and intronic sequences [1]
Focusing on the nervous system, where the impact of AS has been investigated especially well [23,24,25], we argue that isoform co-expression provides an efficient mechanism for generating selfrecognition codes in neurons, modulating protein functions and maintaining gene expression homoeostasis
According to single-cell RT-PCR data, this generates 8–30 distinct Down’s syndrome cell adhesion molecule 1 (Dscam1) splice isoforms co-expressed per neuron at any given time [17,18]
Summary
Alternative pre-mRNA splicing (AS) allows a single gene to generate more than one mature mRNA species through non-uniform utilization of exonic and intronic sequences [1]. For example, during sex determination in Drosophila, where distinct splice isoforms of critical RNA-binding proteins and transcription factors are expressed strictly in a sex-specific manner [5]. Distinct AS isoforms can be expressed in different tissues of the same organism providing an efficient means to adjust protein functions to local physiological requirements [6].
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