Human cells contain natural double-stranded RNAs with potential regulatory functions

Area of Science:

• Molecular Biology
• Genomics
• Cell Biology

Background:

• Sense-antisense transcription suggests RNA complexity beyond single strands.
• The biological role of natural double-stranded RNAs (ndsRNAs) in mammals remains largely unexplored.
• Previous research hinted at, but did not confirm, functional dsRNAs in mammalian cells.

Purpose of the Study:

• To investigate the existence and function of natural double-stranded RNAs (ndsRNAs) in human cells.
• To characterize the cellular localization and protein interactions of identified ndsRNAs.
• To determine the role of specific ndsRNAs, such as nds-2a, in cellular processes, particularly mitosis.

Main Methods:

• Bioinformatic analysis to identify putative ndsRNA candidates from genomic data.
• Cellular localization studies using microscopy.
• Co-immunoprecipitation assays to identify interacting nuclear proteins.
• Functional assays involving manipulation of ndsRNA levels (e.g., nds-2a) to observe cellular effects.

Main Results:

• Hundreds of putative natural double-stranded RNAs (ndsRNAs) were identified, expressed from diverse genomic locations and responsive to cellular signals.
• A subset of ndsRNAs were found to localize in the nucleus and interact with nuclear proteins in their double-stranded form.
• The characterized ndsRNA, nds-2a, interacts with key cell cycle regulators (RCC1, RAN) and the mitotic complex, showing dynamic localization and impacting mitosis.
• Altering nds-2a levels resulted in mitotic catastrophe, cell death, and postmitotic abnormalities.

Conclusions:

• A novel class of functional natural double-stranded RNAs (ndsRNAs) exists in human cells.
• These ndsRNAs, exemplified by nds-2a, are involved in critical cellular processes, including mitosis.
• The discovery of ndsRNAs opens new perspectives on RNA-mediated regulation in human biology and disease.