PARN Modulates Y RNA Stability and Its 3'-End Formation.

Area of Science:

• Molecular Biology
• Genetics
• RNA Metabolism

Background:

• Loss-of-function mutations in 3'-to-5' exoribonucleases are linked to hereditary human diseases.
• PARN mutations cause a severe form of dyskeratosis congenita (DC), leading to human telomerase RNA instability.

Purpose of the Study:

• To investigate the role of PARN in the stability of RNAs beyond telomerase RNA.
• To elucidate the mechanism by which PARN affects Y RNA levels and its contribution to DC.

Main Methods:

• Depletion of PARN, PAPD5, and DIS3L in human cells.
• Deep sequencing of RNA 3' ends.
• Analysis of noncoding RNA levels and 3' end modifications.

Main Results:

• PARN depletion reduces the levels of abundant human Y RNAs.
• Depletion of PAPD5 or DIS3L rescues the Y RNA levels upon PARN depletion.
• PARN deadenylates U6 and RMRP RNAs without affecting their levels.
• Widespread posttranscriptional oligoadenylation, uridylation, and guanylation of U6 and Y RNA 3' ends were observed.

Conclusions:

• PARN stabilizes Y RNAs by removing oligoadenylated tails added by PAPD5, preventing DIS3L-mediated degradation.
• PARN's role in Y RNA stability may contribute to the severe phenotype of dyskeratosis congenita.
• 3' end formation of noncoding RNAs in mammalian cells is a complex process involving multiple polymerases and exonucleases.