An obligate intermediate along the slow folding pathway of a group II intron ribozyme.

Abstract:

:Most RNA molecules collapse rapidly and reach the native state through a pathway that contains numerous traps and unproductive intermediates. The D135 group II intron ribozyme is unusual in that it can fold slowly and directly to the native state, despite its large size and structural complexity. Here we use hydroxyl radical footprinting and native gel analysis to monitor the timescale of tertiary structure collapse and to detect the presence of obligate intermediates along the folding pathway of D135. We find that structural collapse and native folding of Domain 1 precede assembly of the entire ribozyme, indicating that D1 contains an on-pathway intermediate to folding of the D135 ribozyme. Subsequent docking of Domains 3 and 5, for which D1 provides a preorganized scaffold, appears to be very fast and independent of one another. In contrast to other RNAs, the D135 ribozyme undergoes slow tertiary collapse to a compacted state, with a rate constant that is also limited by the formation D1. These findings provide a new paradigm for RNA folding and they underscore the diversity of RNA biophysical behaviors.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Su LJ,Waldsich C,Pyle AM

doi

10.1093/nar/gki973

keywords:

subject

Has Abstract

pub_date

2005-11-27 00:00:00

pages

6674-87

issue

21

eissn

0305-1048

issn

1362-4962

pii

33/21/6674

journal_volume

33

pub_type

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