The IQGAP1-hnRNPM interaction links tumour-promoting alternative splicing to heat-induced signals

Alternative Splicing (AS) is extensively regulated during the cell cycle and is also involved in the progression of distinct cell cycle phases. Stressing agents, such as heat shock, halts AS affecting mainly post-transcriptionally spliced genes. Stress-dependent regulation of AS relies possibly on the subnuclear location of its determinants, such us Serine-Arginine rich (SR) and heterogeneous nuclear ribonucleoproteins, hnRNPs. Spliceosomal components like SRSF1, SRSF9, SRp38, hnRNPM have been connected to such responses of AS, but how they are directed to respond to stress remains largely unknown. Here, we report that upon heat stress, the cytosolic scaffold protein IQGAP1 translocates into the nucleus of gastric cancer cells, where it acts as a tethering module for hnRNPM and other spliceosome components, mediating their subnuclear positioning and their response to stress. Moreover, together, they regulate the AS of the anaphase promoting complex (ANAPC) subunit 10 to promote gastric cancer cell growth.