Join us for an in-person mini-symposium at @qmbci.bsky.social on July 16th to discuss several topics at the intersection of RNA biology and cancer. Free to come. Pizza and drinks to network @diunguyenvnuk.bsky.social @kevinrouault.bsky.social @rnasociety.bsky.social 👇👇

9/12 But what about lncRNA C1QTNF1-AS1? Well, that was a challenging ❓ Since lncRNA did not affect RSRC2 splicing activity, we wondered whether it could affect RSRC2 moonlighting function in mitosis. We found that lncRNA regulates RSRC2 localisation on centrosomes.

8/12 But what is RSRC2 doing on centrosomes? RSRC2 is required for splicing of centrosomal proteins, such as PCNT & CDK5RAP2 & their recruitment on mitotic centrosomes. So mis-splicing of mitotic genes in RSRC2 KD cells is contributing to observed mitotic defects in these cells.

7/12 To understand how RSRC2 regulates splicing, we performed IP MS for RSRC2 and found that splicing and centrosome proteins are top RSRC2 interactors. Thus, RSRC2 is a multifunctional RBP.

6/12 Not much was known about RSRC2 when we started the project.... However, we found RSRC2 to be present in nuclear speckles and to regulate the splicing of mitotic regulators. This fits nicely with RSRC2 being present in Mitocheck and RBP2GO database.

5/12 We found that loss of lncRNA C1QTNF1-AS1 and RSRC2 protein mimic each other since their depletion causes defects in chromosome alignment and mitotic progression.

4/12 To understand how lncRNA C1QTNF1-AS1 regulates cell division, we set out to identify the proteins that C1QTNF1-AS1 interacts with and discover RSRC2, a protein with a poorly defined function.

3/12 How it all started? In our previous work, we identified lncRNA C1QTNF1-AS1, whose loss led to chromosome congression defects and mitotic delay, but we did not know how ❓❓❓

2/12 RSRC2 regulates mitotic fidelity through two distinct mechanisms: one associated with splicing of mitotic regulators and the other by localising to mitotic centrosomes, a function mediated by lncRNA C1QTNF1-AS1.