5/7/2023 0 Comments Def leppard discography![]() ![]() Partners often bind the convex surface of the protein ( Campbell et al., 2012b Edwards et al., 2003 Menichelli et al., 2013 Weidmann et al., 2016 Wu et al., 2013) or intrinsically-disordered N-terminal regions ( Weidmann and Goldstrohm, 2012). As PUF proteins lack detectable enzymatic activity, they require partners to assert their regulatory functions. The 5´ end of the target sequence typically contains a UGU trinucleotide ( Ahringer and Kimble, 1991 Campbell et al., 2012a Dominguez et al., 2018 Galgano et al., 2008 Gerber et al., 2004 Gerber et al., 2006 Hafner et al., 2010 Morris et al., 2008 Wharton and Struhl, 1991 White et al., 2001 Zamore et al., 1997 Zhang et al., 1997). Along the concave face, RNA is bound in a modular fashion. The RNA-binding domain (termed the PUM homology domain) consists of eight α-helical repeats that form a crescent ( Edwards et al., 2001 Jenkins et al., 2009 Miller et al., 2008 Qiu et al., 2012 Wang et al., 2002 Wang et al., 2001 Wang et al., 2009 Weidmann et al., 2016 Wilinski et al., 2015 Zhu et al., 2009). PUF proteins (named for Drosophila melanogaster Pumilio and Caenorhabditis elegans fem-3 Binding Factor) are conserved throughout eukaryotes and support a range of processes including development and neurologic function ( Goldstrohm et al., 2018 Wickens et al., 2002). To interpret mRNA-binding events in cells, understanding how such complexes preferentially recognize their RNA targets is critical. Combinatorial control by multi-protein complexes provides a potential means to diversify regulatory outcomes and to modulate RNA-binding preferences ( Campbell et al., 2012b Hennig et al., 2014 Piqué et al., 2008 Weidmann et al., 2016). Regulation often requires multiple factors that physically interact. RNA-binding proteins recognize discrete structures and sequences present in untranslated regions (UTRs) ( Mayya and Duchaine, 2019). Precise timing of RNA expression, localization, translation and decay permeates virtually every aspect of biology, including pain, memory, and early development ( Bédécarrats et al., 2018 Brinegar and Cooper, 2016 Conlon and Manley, 2017 de la Peña and Campbell, 2018 Kershner et al., 2013 Nussbacher et al., 2019 Shukla and Parker, 2016). RNA-binding proteins control mRNA function. Our findings highlight the role of FBF scaffold flexibility in RNA recognition and suggest a new mechanism by which protein partners refine target site selection. LST-1 weakens FBF-2 binding affinity for short and long motifs, which may increase target selectivity. FBF-2 has the intrinsic ability to bind to this shorter motif. This bias, reflected in the crystal structure, was validated in RNA-binding assays. In vitro selection of RNAs bound by FBF-2 suggested sequence specificity in the central region of the compact element. Previously, we engineered FBF-2 to favor recognition of shorter RNA motifs without curvature change (Bhat et al., 2019). A crystal structure of an FBF-2/LST-1/RNA complex revealed that FBF-2 recognizes a short RNA motif different from the characteristic 9-nt FBF binding element, and compact motif recognition coincided with curvature changes in the FBF-2 scaffold. In the Caenorhabditis elegans germline, fem-3 Binding Factor (FBF) partners with LST-1 to maintain stem cells. ![]()
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