hnRNP D, hnRNP Q and PTB regulates Cap-independent translation of Profilin1

Abstract

Profilin1 is a ubiquitously expressed regulator of actin dynamics. Profilin1 has diverse and critical roles in cell migration, proliferation, signaling and cell survival through actin cytoskeletal regulation. Moreover, profilin1 is also important for axonal outgrowth and spinogenesis of neurons. Lack of profilin1 shortens axon length and inhibit spine formation. Thus, identifying the regulation mechanisms of profilin1 is essential. However, the regulation mechanisms of profilin1 remains still unknown. Here, we observed that profilin1 mRNA is translated by both cap-dependent and cap-independent initiation mechanisms. The cap-independent translation of profilin1 is regulated by hnRNP Q, hnRNP D and PTB. We confirmed that they binds to the 5’UTR of profilin1 mRNA. Knock-down of hnRNP Q and hnRNP D increased profilin1 mRNA translation. PTB knock-down inhibit the cap-independent translation of profilin1. Thus, our findings suggest that hnRNP Q and hnRNP D function as negative regulators and PTB functions as a positive regulator. Our findings suggest a new translational regulatory mechanism for profilin1 expressions.2