Temporal order of interaction directs native assembly of the mammalian signal recognition particle

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  • March 22, 2019
Creator
  • Maity, Tuhin Subhra
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Assembly of most ribonucleoproteins (RNPs) proceeds via multi-step structural reorganization in both protein and RNA components. To date, essentially all assembly models for RNP have tacitly assumed that structural interaction between any two given components during an RNP formation either facilitates later steps in the assembly or has no effect on continued assembly. In contrast to this implicit hypothesis, this work reveals that untimely interaction between components may, in fact, disrupt native formation of an RNP. In the assembly of the mammalian signal recognition particle (SRP), SRP54 interacts with the preformed SRP19-SRP RNA complex to form the native SRP ternary complex. In contrast, if SRP54 interacts with the RNA prior to formation of the native SRP19-SRP RNA complex, these three components interact to form an alternate ternary complex. In this complex, two extended loops in SRP19 cannot natively interact with the RNA. It has been shown that the premature RNA binding by SRP54 alters the SRP19- RNA assembly energy landscape in such a way that an alternate SRP19-RNA folding pathway leading to non-native complex formation becomes kinetically prevalent. In a different instance, it has been found that prior RNA binding by SRP68/72 negatively affects assembly of SRP19 with the SRP RNA, and vice versa. Experimental results support a model in which structural tension between two similar but slightly distinct RNA structures induced by SRP19 and SRP68/72 binding is the origin of such anticooperativity. Overall, this work suggests that the order by which each constituent in an RNP interacts with others during assembly may have a decisive role in formation of the native complex. It has been inferred in this work that idiosyncratic assembly mechanisms, such as cellular compartmentalization and preferred early and late assembly phases, may play critical regulatory roles in preventing order-of-interaction driven misassembly for many multi-component RNPs in the cell.
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  • In Copyright
Advisor
  • Weeks, Kevin
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
Date uploaded
  • October 19, 2010

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