Alternatively spliced isoforms of the human elk-1 mRNA within the 5′ UTR: implications for ELK-1 expression

Abstract

The expression of cellular proteins that play central roles in the regulation of cell growth and differentiation is frequently tightly controlled at the level of translation initiation. In this article, we provide evidence that the ETS domain transcription factor ELK-1 forms part of this class of genes. Its mRNA 5′ UTR is composed of a complexed mosaic of elements, including uAUGs, uORFs and RNA structure, that interplay to modulate ribosomal access to the ELK-1 AUG start codon. Superimposed upon this is the generation of two different 5′ UTRs via alternative splicing. The two spliced isoforms show altered cellular and tissue distributions and behave differently in polysomal recruitment assays in the presence of the drug rapamycin. We propose that repression is therefore the sum of a series of interplaying negative elements within the 5′ UTRs, a situation which may reflect the need for tight translational control of ELK-1 in different tissues and under changing physiological conditions.

The Current Status of Vertebrate Cellular mRNA IRESs

“…Thus far, only the Types I and II picornavirus IRESs (exemplified by EMCV and HRV) consistently come close to meeting this criterion (Bert et al 2006;Araud et al 2007;Andreev et al 2009). There are also single reports in which the Unr 5…”

“…0 -UTR (albeit tested with FLuc as the upstream cistron) and DAP5 5 0 -UTR met this criterion (Araud et al 2007;Schepens et al 2007), but in view of the ESTevidence for 3 0 -splice sites in both cases (Baranick et al 2008), independent confirmation of these findings is desirable. At the other extreme, the HIF-1a, VEGF, XIAP, and EGR-1 5 0 -UTRs comprehensively failed the siRNA test (Bert et al 2006).…”

Novel splice variant of mouse insulin2 mRNA: Implications for insulin expression

“…Similarly, intron1 of Rat insulin1 increases the expression of reporter gene, by regulating the transcription and processing [20]. 5 0 UTR sequences have been reported to regulate translation by secondary structure formation and uORFs [21]. Alternative transcription start site of embryonic insulin mRNA results in a longer 5 0 UTR containing upstream AUGs, resulting in very low level translation of the proinsulin [22].…”

Decoding sORF translation – from small proteins to gene regulation

“…Mechanisms generating transcript isoforms differing in the number and/or location of uORFs include alternative transcription start site (TSS) usage 92,107,112,113 and alternative splicing. [114][115][116][117][118] The impact that a different transcript leader can have on protein production is exemplified by the disease-causing splice donor mutation in the Thrombopoietin (THPO) transcript leader. 119 Exon-skipping generates a THPO transcript leader lacking uORFs.…”