Abstract
Alternative translation is an important mechanism of post-transcriptional gene regulation leading to the expression of different protein isoforms originating from the same mRNA. Here, we describe an abundant long isoform of the stress/p38MAPK-activated protein kinase MK2. This isoform is constitutively translated from an alternative CUG translation initiation start site located in the 5' UTR of its mRNA. The RNA helicase eIF4A1 is needed to ensure translation of the long and the known short isoforms of MK2, of which the molecular properties were determined. Only the short isoform phosphorylated Hsp27 invivo, supported migration and stress-induced immediate early gene (IEG) expression. Interaction profiling revealed short-isoform-specific binding partners that were associated with migration. In contrast, the long isoform contains at least one additional phosphorylatable serine in its unique N terminus. In sum, our data reveal a longer isoform of MK2 with distinct physiological properties.
Highlights
Post-transcriptional gene regulation (PTGR) constitutes an important toolbox used to shape gene expression upon intraand extracellular cues
Alternative translation is an important mechanism of post-transcriptional gene regulation leading to the expression of different protein isoforms originating from the same mRNA
We describe an abundant long isoform of the stress/p38MAPK-activated protein kinase MK2. This isoform is constitutively translated from an alternative CUG translation initiation start site located in the 50 UTR of its mRNA
Summary
Post-transcriptional gene regulation (PTGR) constitutes an important toolbox used to shape gene expression upon intraand extracellular cues. The entire translation initiation mechanism is tightly regulated (Sonenberg and Hinnebusch, 2009) and can be influenced by sequences in the 50 UTR-bearing internal ribosomal entry sites (IRESs), secondary structures, or upstream open reading frames (uORFs) or by ‘‘leaky scanning’’ of sequences preceding the initiator AUG (Kozak sequence), leading to the usage of alternative start codons that result in alternative protein isoform translation (Barbosa et al, 2013; Fritsch et al, 2012; Hinnebusch et al, 2016). Translation events starting at these non-AUG start codons have led to the determination of alternative translation initiation sites (aTISs) (Wan and Qian, 2014; Wegrzyn et al, 2008). Taken together, these features of translation explain, in part, how proteome diversity in cells can be generated from a limited number of transcripts
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