Antagonism between splicing and microprocessor complex dictates the serum-induced processing of lnc-MIRHG for...

Area of Science:

• Molecular Biology
• Genomics
• Cell Biology

Background:

• Cellular quiescence and cell cycle reentry are crucial for development and homeostasis, governed by gene expression.
• The role of long noncoding RNAs (lncRNAs) in these processes is not fully understood.
• MicroRNA-host-gene (MIRHG) lncRNAs are a less-characterized class with potential regulatory functions.

Purpose of the Study:

• To investigate the role of lncRNAs in cellular quiescence and cell cycle reentry.
• To identify specific lncRNAs involved in these processes.
• To elucidate the regulatory mechanisms controlling lncRNA processing and function during cell cycle transitions.

Main Methods:

• Genome-wide transcriptome analysis to identify differentially expressed lncRNAs.
• RNA processing assays to study MIR222HG splicing and microRNA processing.
• Co-immunoprecipitation and RNA stability assays to investigate lncRNA interactions and complex formation.

Main Results:

• Hundreds of lncRNAs, including MIRHG lncRNAs, are differentially expressed during quiescence and reentry.
• MIR222HG lncRNA processing is serum-stimulated via enhanced splicing, regulated by SRSF1.
• Spliced MIR222HG promotes cell cycle reentry independently of microRNA activity, interacting with DNM3OS.
• The ILF3/2 complex stabilizes the MIR222HG:DNM3OS complex.

Conclusions:

• A novel mechanism involving competition between splicing and microprocessor machinery regulates MIR222HG processing.
• This regulation dictates cell cycle reentry post-quiescence.
• MIR222HG and DNM3OS play critical roles in promoting cell cycle reentry through a microRNA-independent pathway.