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Mol Cell. 2019 Nov 5. pii: S1097-2765(19)30766-X. doi: 10.1016/j.molcel.2019.10.006. [Epub ahead of print]

The Biogenesis of SRP RNA Is Modulated by an RNA Folding Intermediate Attained during Transcription.

Author information

1
Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA; Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Science, Tokyo, Japan; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan. Electronic address: shingof0617@gmail.com.
2
Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. Electronic address: shannonyan@berkeley.edu.
3
Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA; Laboratory for Protein Conformation Diseases, RIKEN Center for Brain Science, Wako, Saitama, Japan.
4
Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
5
Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA.
6
Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Jason L. Choy Laboratory of Single-Molecule Biophysics, University of California, Berkeley, Berkeley, CA, USA; Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA; Department of Physics, University of California, Berkeley, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA; Kavli Energy Nanoscience Institute, University of California, Berkeley, Berkeley, CA, USA. Electronic address: carlosb@berkeley.edu.

Abstract

The signal recognition particle (SRP), responsible for co-translational protein targeting and delivery to cellular membranes, depends on the native long-hairpin fold of its RNA to confer functionality. Since RNA initiates folding during its synthesis, we used high-resolution optical tweezers to follow in real time the co-transcriptional folding of SRP RNA. Surprisingly, SRP RNA folding is robust to transcription rate changes and the presence or absence of its 5'-precursor sequence. The folding pathway also reveals the obligatory attainment of a non-native hairpin intermediate (H1) that eventually rearranges into the native fold. Furthermore, H1 provides a structural platform alternative to the native fold for RNase P to bind and mature SRP RNA co-transcriptionally. Delays in attaining the final native fold are detrimental to the cell, altogether showing that a co-transcriptional folding pathway underpins the proper biogenesis of function-essential SRP RNA.

KEYWORDS:

RNA maturation; SRP; SRP RNA; co-transcriptional RNA-folding trajectory; folding intermediates; optical tweezers; signal recognition particle; single-molecule analysis; transcription

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