Mechano-Regulation of Alternative Splicing

Abstract

Alternative splicing contributes to the complexity of proteome by producing multiple mRNAs from a single gene. Affymetrix exon arrays and experiments in vivo or in vitro demonstrated that alternative splicing was regulated by mechanical stress. Expression of mechano-growth factor (MGF) which is the splicing isoform of insulin-like growth factor 1(IGF-1) and vascular endothelial growth factor (VEGF) splicing variants such as VEGF121, VEGF165, VEGF206, VEGF189, VEGF165 and VEGF145 are regulated by mechanical stress. However, the mechanism of this process is not yet clear. Increasing evidences showed that the possible mechanism is related to Ca2+ signal pathway and phosphorylation signal pathway. This review proposes possible mechanisms of mechanical splicing regulation. This will contribute to the biomechanical study of alternative splicing.

Dissecting the Effect of a 3D Microscaffold on the Transcriptome of Neural Stem Cells with Computational Approaches: A Focus on Mechanotransduction

“…Lastly, we show that the mechanically induced effect on cell biology also implicates the nucleus, as mechanotransduction can modulate the shape and the structure of the nucleus in response to changes in the interaction between cytoskeleton and nucleoskeleton [74]. We found multiple nuclear processes involved (DNA repair mechanisms, modulation of transcription, regulation of molecule transport through nuclear membrane, RNA metabolism, and activation of specific mechanosensitive gene), all already linked to mechanotransduction processes [78][79][80][81][82][83][84][85][86][87]. We assessed the differences in cytoskeleton organization and adhesion complexes formation evaluating the specific deregulation in genes' pertaining to these processes, along with a morphological analysis with immunofluorescence and ESEM technology.…”

“…Spliceosome, mRNA processing, mRNA surveillance pathway, and RNA degradation are processes that control every step of an RNA molecule life deeply affecting the cell fate ( Figure 5 C,D). Indeed, splicing and quality control mechanism can also be controlled by mechanotransduction [ 86 , 87 ].…”

Mechanical Stress and Single Nucleotide Variants Regulate Alternative Splicing of the MYLK Gene

“…Analysis of point mutations at the splice site at the splice junction has been shown to directly affect mRNA splicing (52). On the other hand, mechanical stretch has been shown to directly affect alternate splicing of tenascin, collagen XII, and versican, which are attributed to alteration of calcium signaling and to mechanical signals transmitted from the exterior of the cell to the interior through the Integrin, FAK, and ERK pathways (53).…”

Genetic mutations potentially cause two novel NCF1 splice variants up-regulated in the mammary gland, blood and neutrophil of cows infected by Escherichia coli

“…Many cis-elements which embedded in pre-mRNAs and trans-acting bound to these elements are required to splice and regulate the pre-mRNA (Singh and Cooper, 2012). These elements, are known as spliceosome that consist of five small nuclear ribonucleoprotein particles (U1, U2, U4, U5 and U6 snRNPs) and approximately 200 proteins (Liu and Tang, 2013). The short sequences that are located at the intron-exon junctions include the branch point, 5 -splice sites and 3 -splice sites (Irimia and Blencowe, 2012).…”