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.
Summary
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.
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.
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