Identification of antisense long noncoding RNAs that function as SINEUPs in human cells

Area of Science:

• Molecular Biology
• Genomics
• RNA Biology

Background:

• Mammalian genomes contain natural antisense long noncoding RNAs (lncRNAs) involved in gene expression regulation.
• A novel class of lncRNAs, SINEUPs (SINE element-containing translation UP-regulators), was recently identified for their role in enhancing protein synthesis.

Purpose of the Study:

• To investigate the function of an antisense lncRNA to human PPP1R12A, named R12A-AS1.
• To determine if R12A-AS1 acts as a SINEUP, enhancing PPP1R12A protein translation in human cells.
• To identify other human antisense lncRNAs with SINEUP activity.

Main Methods:

• Characterization of the R12A-AS1 lncRNA, including its overlap with the PPP1R12A mRNA.
• Experimental validation of R12A-AS1's role in increasing PPP1R12A protein translation.
• Analysis of the structural requirements for SINEUP activity, including sense-antisense interaction and Alu elements.

Main Results:

• R12A-AS1 functions as a SINEUP, significantly increasing PPP1R12A protein translation in human cells.
• SINEUP activity of R12A-AS1 is dependent on the sense-antisense interaction and a specific Alu monomer repeat.
• Another human antisense lncRNA exhibiting SINEUP activity was identified.

Conclusions:

• Human natural antisense lncRNAs can actively up-regulate protein translation, expanding the known functions of lncRNAs.
• Endogenous SINEUPs are likely prevalent in human cells and potentially widespread across mammalian species.
• This discovery opens new avenues for understanding gene regulation and therapeutic target identification.