Moderate activity of RNA chaperone maximizes the yield of self-spliced pre-RNA in vivo

Author:

Song Yonghyun1ORCID,Thirumalai D.2ORCID,Hyeon Changbong1ORCID

Affiliation:

1. Korea Institute for Advanced Study, Seoul 02455, Korea

2. Department of Chemistry, The University of Texas at Austin, Austin, TX 78712

Abstract

CYT-19 is a DEAD-box protein whose adenosine-triphosphate (ATP)-dependent helicase activity facilitates the folding of group I introns in precursor RNA (pre-RNA) of Neurospora crassa ( N. crassa ). In the process, they consume a substantial amount of ATP. While much of the mechanistic insight into CYT-19 activity has been gained through the studies on the folding of Tetrahymena group I intron ribozyme, the more biologically relevant issue, namely the effect of CYT-19 on the self-splicing of pre-RNA, remains largely unexplored. Here, we employ a kinetic network model, based on the generalized iterative annealing mechanism (IAM), to investigate the relation between CYT-19 activity, rate of ribozyme folding, and the kinetics of the self-splicing reaction. The network rate parameters are extracted by analyzing the recent biochemical data for CYT-19-facilitated folding of Tetrahymena ribozyme. We then build extended models to explore the metabolism of pre-RNA. We show that the timescales of chaperone-mediated folding of group I ribozyme and self-splicing reaction compete with each other. As a consequence, in order to maximize the self-splicing yield of group I introns in pre-RNA, the chaperone activity must be sufficiently large to unfold the misfolded structures, but not too large to unfold the native structures prior to the self-splicing event. We discover that despite the promiscuous action on structured RNAs, the helicase activity of CYT-19 on group I ribozyme gives rise to self-splicing yields that are close to the maximum.

Funder

KIAS

National Science Foundation

Welch Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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