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Intronic polyadenylation-derived long noncoding RNA modulates nucleolar integrity and function.

Sumana Mallick1,2, Pranita Borkar1, Jaspreet Thind1,2

  • 1Department of Cell Biology and Genetics, Texas A&M University Health Science Center, Bryan, TX 77807.

Proceedings of the National Academy of Sciences of the United States of America
|January 30, 2026
PubMed
Summary
This summary is machine-generated.

Intronic polyadenylation (IPA) generates noncoding RNAs like CUL1-IPA. This long noncoding RNA maintains nucleolar integrity, supports rRNA processing, and impacts cell cycle progression and cancer patient survival.

Keywords:
intronic polyadenylationlong noncoding RNAnucleolus

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Protein-coding genes typically produce mRNA for translation.
  • Intronic polyadenylation (IPA) near transcription start sites generates noncoding RNAs from protein-coding loci.
  • The functions of these abundant IPA-derived noncoding RNAs are largely unknown.

Purpose of the Study:

  • To investigate the function of CUL1-IPA, a noncoding RNA derived from the CUL1 gene locus via IPA.
  • To explore the role of CUL1-IPA in cellular processes, particularly nucleolar function and its potential implications in disease.

Main Methods:

  • Identified CUL1-IPA as an RNA polymerase II-dependent, stable, polyadenylated noncoding RNA.
  • Assessed CUL1-IPA's localization and functional role in maintaining nucleolar integrity.
  • Utilized RNA-protein interaction assays to identify binding partners.
  • Quantified rRNA levels, protein synthesis, and cell cycle progression upon CUL1-IPA manipulation.
  • Analyzed CUL1-IPA expression in cancer patient data.

Main Results:

  • CUL1-IPA translocates to the nucleolus and is critical for its integrity.
  • GPATCH4 and NOP58, involved in rRNA processing, were identified as CUL1-IPA binding partners.
  • Loss of CUL1-IPA reduced rRNA levels, decreased protein synthesis, and caused G2/M cell cycle arrest.
  • Reintroduction of CUL1-IPA restored rRNA levels.
  • Reduced CUL1-IPA expression correlated with improved survival in cancer patients.

Conclusions:

  • CUL1-IPA is a functional long noncoding RNA (lncRNA) originating from a protein-coding gene via IPA.
  • CUL1-IPA forms nucleolar RNA-protein complexes essential for rRNA processing and nucleolar structure.
  • This lncRNA plays a significant role in cellular homeostasis and has implications for cancer patient outcomes.