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Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins.

Huang Wu1, Qing-Fei Yin2, Zheng Luo3

  • 1State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Molecular Cell
|November 23, 2016
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Summary
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Researchers discovered novel long noncoding RNAs (lncRNAs) called SPAs, processed from polycistronic transcripts. These SPAs are linked to Prader-Willi syndrome (PWS) and influence RNA binding protein interactions and splicing.

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Area of Science:

  • Molecular Biology
  • Genetics
  • RNA Biology

Background:

  • Long noncoding RNAs (lncRNAs) play crucial roles in gene regulation.
  • Polycistronic transcripts are common in some organisms but less understood in mammals.
  • Prader-Willi syndrome (PWS) is a complex genetic disorder with poorly understood molecular mechanisms.

Purpose of the Study:

  • To identify and characterize a novel class of lncRNAs derived from polycistronic transcripts.
  • To investigate the biogenesis and function of these lncRNAs.
  • To explore the potential role of these lncRNAs in the pathogenesis of Prader-Willi syndrome.

Main Methods:

  • Identification and sequencing of polycistronic transcript-derived lncRNAs.
  • Biochemical assays to study RNA processing and protein interactions.
  • Generation and analysis of a human cellular model for PWS by lncRNA depletion.

Main Results:

  • Discovery of 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated (SPA) lncRNAs.
  • SPA biogenesis involves competition between XRN2 trimming and Pol II elongation, with snoRNPs halting degradation.
  • Two SPAs encoded in the 15q11-q13 region are deleted in PWS patients and interact with RNA binding proteins (RBPs) like TDP43.
  • Depletion of these SPAs in a PWS model alters RBP binding and alternative splicing patterns.

Conclusions:

  • SPAs represent a newly identified class of lncRNAs with unique processing mechanisms.
  • These SPAs are implicated in PWS pathogenesis through their interactions with RBPs and influence on splicing.
  • The findings expand the known diversity of lncRNAs and offer new insights into PWS etiology.