Session 12 and Closing Remarks

Approximately half of human genes use alternative polyadenylation to generate mRNA isoforms with identical coding region but with alternative 3′ untranslated regions (3′UTRs). We quantified alternative 3′UTRs in more than 100 cell types and observed that hundreds of genes change their 3′UTR isoform expression in a coordinated manner during differentiation. Intriguingly, the majority of these genes (~85%) did not change their mRNA abundance level at the same time. This indicates that we identified hundreds of genes that have never been implicated in these processes, but for the majority of them it is currently unclear what a change in 3′UTR isoform expression means.
Over the last five years, we found that 3′UTRs – despite not being part of proteins – regulate protein localization, protein activity, and protein function. In the case of alternative 3′UTRs, we discovered that they diversify protein function without changing the amino acid sequence. Mechanistically, 3′UTR-dependent regulation of protein function occurs through 3′UTR-mediated protein complex formation as we identified protein complexes that can only be established in the presence of specific 3′UTRs. We showed that in some cases 3′UTRs act as scaffolds and recruit potential interactors to the site of translation, thus promoting co-translational protein-protein interactions. In other cases, 3′UTRs enable protein translation in specific phase-separated cytoplasmic compartments thus allowing formation of certain protein complexes that cannot be established upon translation outside of such compartments.
Taken together, we found that protein complex formation mediated by 3′UTRs relies less on overall cellular interactor abundance but instead takes advantage of the effective local concentration and possibly a specific solvent environment. Our results indicate that many proteins have several functions. Some of them are autonomous and are predominantly regulated by abundance, whereas other functions are non-autonomous and are dictated by regulatory elements in 3′UTRs.

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Mosquitoes are the most dangerous animal in the world. Diseases spread by one invasive mosquito, Aedes (Ae) aegypti, are on the rise and afflict ~400 million people each year. Female Ae. aegypti, depend on multiple sensory stimuli such as vision, CO2 and organic compounds to zero in on humans for blood meals. Over decades, no other cues have been found that mosquitoes use to target people. We discovered that that infrared (IR) radiation emanating from people is sensed by Ae. aegypti and used as part of their sensory detection arsenal to locate human hosts. The ability to detect IR radiation is dependent in part on the TRPA1 channel. Remarkably, two opsins, which were formerly thought to function exclusively in light sensation are also required for IR detection. We propose that the discovery of IR radiation as a new type attractive sensory cue used by mosquitoes will enable the development of innovative approaches to limit their ability to locate people, and to devise better mosquito traps to control mosquito populations.