Journal:MicroPubl Biol:000606
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RNA helicases comprise a large family of proteins involved in nearly all aspects of RNA function, including ribosome assembly and translation. Historically, the main ascribed function of helicases is to unwind (i.e. unzip) DNA and RNA duplexes, though their function is now recognized to include the association, dissociation, or remodeling of RNA-RNA and RNA-protein complexes. The focus of our article, Utp25, was first discovered as a component of the small subunit (SSU) processome, a 6 MDa ribonucleoprotein complex responsible for most pre-rRNA processing and assembly steps of the SSU of the ribosome <ref name='CharetteBaserga2010'/><ref name='GoldfederOliveira2010'/>). Sequence analysis identified in Utp25 partial sequence motifs (Figure 1-Top) that are hallmarks of the DEAD-box family of RNA helicases. These conserved motifs mediate the binding of RNA and/or the binding and hydrolysis of ATP. Interestingly, Utp25 has significant sequence changes in most of these motifs. Mutational loss of the remaining conserved sequence motifs 1a and partial motif VI resulted in no change in growth <ref name='CharetteBaserga2010'/>. | RNA helicases comprise a large family of proteins involved in nearly all aspects of RNA function, including ribosome assembly and translation. Historically, the main ascribed function of helicases is to unwind (i.e. unzip) DNA and RNA duplexes, though their function is now recognized to include the association, dissociation, or remodeling of RNA-RNA and RNA-protein complexes. The focus of our article, Utp25, was first discovered as a component of the small subunit (SSU) processome, a 6 MDa ribonucleoprotein complex responsible for most pre-rRNA processing and assembly steps of the SSU of the ribosome <ref name='CharetteBaserga2010'/><ref name='GoldfederOliveira2010'/>). Sequence analysis identified in Utp25 partial sequence motifs (Figure 1-Top) that are hallmarks of the DEAD-box family of RNA helicases. These conserved motifs mediate the binding of RNA and/or the binding and hydrolysis of ATP. Interestingly, Utp25 has significant sequence changes in most of these motifs. Mutational loss of the remaining conserved sequence motifs 1a and partial motif VI resulted in no change in growth <ref name='CharetteBaserga2010'/>. | ||
| - | Using the AlphaFold predicted yeast Utp25 structure as a query, we used Dali to search for proteins with a similar structure. Our top hits were to other DEAD-box helicases including the prototypical RNA helicase eIF4A. We then used Chimera to structurally align Utp25 and eIF4a. By independently aligning the structures of <scene name='92/920755/Cv/4'>domain 1</scene> from Utp25 (gold) and eIF4A (purple) and similarly of domain 2, we show that Utp25 globally adopts a structure that is very similar to that of DEAD-box RNA helicases (Figure 1-Middle, File 1 and 2). Examination of the helicase motifs similarly shows that they are superimposable, except for motif 1c (Figure 1-Bottom). This local structural similarity has been maintained despite the sequence divergence of the helicase motifs in Utp25 (except for motif Ia and partial motif VI that have maintained sequence conservation). Thus, we propose that Utp25 is a pseudohelicase based on it being an essential protein that adopts a helicase structure - both globally and locally - while having lost the catalytic sequence motifs (with remaining motifs being dispensable). | + | Using the AlphaFold predicted yeast Utp25 structure as a query, we used Dali to search for proteins with a similar structure. Our top hits were to other DEAD-box helicases including the prototypical RNA helicase eIF4A. We then used Chimera to structurally align Utp25 and eIF4a. By independently aligning the structures of <scene name='92/920755/Cv/4'>domain 1</scene> from Utp25 (gold) and eIF4A (purple) and similarly of <scene name='92/920755/Cv/7'>domain 2</scene>, we show that Utp25 globally adopts a structure that is very similar to that of DEAD-box RNA helicases (Figure 1-Middle, File 1 and 2). Examination of the helicase motifs similarly shows that they are superimposable, except for motif 1c (Figure 1-Bottom). This local structural similarity has been maintained despite the sequence divergence of the helicase motifs in Utp25 (except for motif Ia and partial motif VI that have maintained sequence conservation). Thus, we propose that Utp25 is a pseudohelicase based on it being an essential protein that adopts a helicase structure - both globally and locally - while having lost the catalytic sequence motifs (with remaining motifs being dispensable). |
What might Utp25s function be as a pseudohelicase? We propose that Utp25 is a helicase co-factor that provides sequence/substrate specificity to a SSU processome helicase such as Dhr2. RNA helicases possess non-specific RNA binding activity and rely instead on a protein co-factor that binds to specific RNA sequence or secondary structure elements and recruits the RNA helicase to the target region through protein-protein interactions and stimulates its helicase activity. | What might Utp25s function be as a pseudohelicase? We propose that Utp25 is a helicase co-factor that provides sequence/substrate specificity to a SSU processome helicase such as Dhr2. RNA helicases possess non-specific RNA binding activity and rely instead on a protein co-factor that binds to specific RNA sequence or secondary structure elements and recruits the RNA helicase to the target region through protein-protein interactions and stimulates its helicase activity. | ||
Revision as of 11:43, 30 August 2022
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