Structural accommodations accompanying splicing of a group II intron RNP

Nucleic Acids Res. 2018 Sep 19;46(16):8542-8556. doi: 10.1093/nar/gky416.

Abstract

Group II introns, the putative progenitors of spliceosomal introns and retrotransposons, are ribozymes that are capable of self-splicing and DNA invasion. In the cell, group II introns form ribonucleoprotein (RNP) complexes with an intron-encoded protein, which is essential to folding, splicing and retromobility of the intron. To understand the structural accommodations underlying splicing, in preparation for retromobility, we probed the endogenously expressed Lactococcus lactis Ll.LtrB group II intron RNP using SHAPE. The results, which are consistent in vivo and in vitro, provide insights into the dynamics of the intron RNP as well as RNA-RNA and RNA-protein interactions. By comparing the excised intron RNP with mutant RNPs in the precursor state, confined SHAPE profile differences were observed, indicative of rearrangements at the active site as well as disengagement at the functional RNA-protein interface in transition between the two states. The exon-binding sequences in the intron RNA, which interact with the 5' exon and the target DNA, show increased flexibility after splicing. In contrast, stability of major tertiary and protein interactions maintains the scaffold of the RNA through the splicing transition, while the active site is realigned in preparation for retromobility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Exons / genetics
  • Introns / genetics*
  • Lactococcus lactis / genetics*
  • Lactococcus lactis / metabolism
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Protein Binding
  • RNA Splicing*
  • RNA, Catalytic / chemistry
  • RNA, Catalytic / genetics
  • RNA, Catalytic / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics*
  • Ribonucleoproteins / metabolism
  • Spliceosomes / genetics
  • Spliceosomes / metabolism

Substances

  • Bacterial Proteins
  • RNA, Catalytic
  • Ribonucleoproteins