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bioRxiv · 10.1101/2022.02.11.480102

Polymorphic ribonucleoprotein folding as a basis for translational regulation

Dendooven, T.·Sonnleitner, E.·Blasi, U.·Luisi, B.
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Abstract

The widely occurring bacterial RNA chaperone Hfq is a key factor in the post-transcriptional control of hundreds of genes in Pseudomonas aeruginosa. How this broadly acting protein can contribute to the regulation requirements of so many different genes remains puzzling. Here, we describe the structures of higher-order assemblies formed on control regions of different P. aeruginosa target mRNAs by Hfq and its partner protein Crc. Our results show that these assemblies have mRNA-specific quaternary architectures resulting from the combination of multivalent protein-protein interfaces and recognition of patterns in the RNA sequence. The structural polymorphism of the ribonucleoprotein assemblies enables selective translational repression of many different target mRNAs. This system suggests how highly complex regulatory pathways can evolve and be rewired with a simple economy of proteinogenic components. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/480102v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1b34242org.highwire.dtl.DTLVardef@1c31071org.highwire.dtl.DTLVardef@16c8750org.highwire.dtl.DTLVardef@27ca3c_HPS_FORMAT_FIGEXP M_FIG C_FIG The RNA chaperone Hfq, in conjunction with the co-repressor Crc, forms higher order assemblies on nascent mRNAs. These complexes impact on translation of hundreds of transcripts in the pathogen Pseudomonas aeruginosa. Assemblies with different quaternary structures result from the interactions of the proteins with sequence motifs and structural elements in different mRNA targets, as well as from a repertoire of protein-to-protein interfaces. In this way, the combination of RNA sequence and two proteins can generate the diversity required to regulate many genes. It is proposed that the multi-step assembly process is highly cooperative and most likely competes kinetically with translation initiation to silence the targeted transcripts.

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Dendooven, T., Sonnleitner, E., Blasi, U., Luisi, B.. 2022-02-12. Polymorphic ribonucleoprotein folding as a basis for translational regulation. https://doi.org/10.1101/2022.02.11.480102

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