Intron Retention Controls Localization of lncRNAs PURPL and MALAT1 to Promote Cell Proliferation and Migration

Area of Science:

• Molecular Biology
• Genetics
• RNA Biology

Background:

• Intron retention (IR) is a splicing event where introns persist in mature RNA.
• The molecular mechanisms driving widespread IR in lncRNAs are not fully understood.

Purpose of the Study:

• To investigate the mechanisms of IR in the lncRNA PURPL using a genome-wide screen.
• To identify factors that regulate IR in lncRNAs.

Main Methods:

• CRASP-seq: A novel genome-wide screen for IR mechanisms.
• RNA-binding analysis to identify U2AF2 binding sites.
• Depletion studies to assess U2AF2 function.
• Functional assays for MALAT1 localization and cell migration.

Main Results:

• CRASP-seq identified U2AF2 as a key regulator promoting IR in PURPL by binding to a weak polypyrimidine tract.
• U2AF2 was also found to promote IR in MALAT1, affecting its nuclear speckle localization.
• Retention of a specific MALAT1 intron was crucial for its localization and promoting cell migration.

Conclusions:

• U2AF2 exhibits a non-canonical function in promoting IR.
• IR plays a critical role in the subcellular localization and function of lncRNAs like PURPL and MALAT1.
• This study reveals novel insights into the regulation and functional consequences of IR in lncRNAs.