23,450 research outputs found

    Gene length as a regulator for ribosome recruitment and protein synthesis : theoretical insights

    Get PDF
    The authors would like to acknowledge the funding provided by the European Union Seventh Framework Programme [FP7/2007–2013] (NICHE; grant agreement 289384) (LDF). LDF also acknowledges the funding provided by the São Paulo Research Foundation (FAPESP - grant #2015/26989-4). AM was partially funded by the UK Biotechnology and Biological Research Council (BBSRC), through grant BB/N015711/1. LC would like to acknowledge Maria Carmen Romano, Jean Hausser, Marco Cosentino Lagomarsino, Jean-Charles Walter and Norbert Kern for early discussions on this work, and the CNRS for having granted him a “demi-délégation” (2017–18). We would like to dedicate this work in memory of Maxime Clusel and Vladimir Lorman.Peer reviewedPublisher PDFPublisher PD

    Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability.

    Get PDF
    HIV-1 Rev is an essential viral regulatory protein that facilitates the nuclear export of intron-containing viral mRNAs. It is organized into structured, functionally well-characterized motifs joined by less understood linker regions. Our recent competitive deep mutational scanning study confirmed many known constraints in Rev's established motifs, but also identified positions of mutational plasticity, most notably in surrounding linker regions. Here, we probe the mutational limits of these linkers by testing the activities of multiple truncation and mass substitution mutations. We find that these regions possess previously unknown structural, functional or regulatory roles, not apparent from systematic point mutational approaches. Specifically, the N- and C-termini of Rev contribute to protein stability; mutations in a turn that connects the two main helices of Rev have different effects in different contexts; and a linker region which connects the second helix of Rev to its nuclear export sequence has structural requirements for function. Thus, Rev function extends beyond its characterized motifs, and is tuned by determinants within seemingly plastic portions of its sequence. Additionally, Rev's ability to tolerate many of these massive truncations and substitutions illustrates the overall mutational and functional robustness inherent in this viral protein
    corecore