Two-step mechanism for selective incorporation of lncRNA into a chromatin modifier

Nucleic Acids Res. 2020 Jul 27;48(13):7483-7501. doi: 10.1093/nar/gkaa492.


The MLE DExH helicase and the roX lncRNAs are essential components of the chromatin modifying Dosage Compensation Complex (DCC) in Drosophila. To explore the mechanism of ribonucleoprotein complex assembly, we developed vitRIP, an unbiased, transcriptome-wide in vitro assay that reveals RNA binding specificity. We found that MLE has intrinsic specificity for U-/A-rich sequences and tandem stem-loop structures and binds many RNAs beyond roX in vitro. The selectivity of the helicase for physiological substrates is further enhanced by the core DCC. Unwinding of roX2 by MLE induces a highly selective RNA binding surface in the unstructured C-terminus of the MSL2 subunit and triggers-specific association of MLE and roX2 with the core DCC. The exquisite selectivity of roX2 incorporation into the DCC thus originates from intimate cooperation between the helicase and the core DCC involving two distinct RNA selection principles and their mutual refinement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cloning, Molecular / methods
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome*


  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • Pabp2 protein, Drosophila
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Transcription Factors
  • mle protein, Drosophila
  • DNA Helicases