TRNAU1AP and PRPF39 establish integrated control over processing of most abundant human non-coding RNAs

Area of Science:

• Molecular Biology
• RNA Processing
• Gene Regulation

Background:

• The maturation of metastasis-associated long non-coding RNA MALAT1 relies on its 3' end processing.
• The specific mechanisms controlling this crucial step were previously unknown.

Purpose of the Study:

• To identify the factors and pathways regulating the 3'-end processing of MALAT1.
• To elucidate the broader impact of this regulatory pathway on cellular RNA metabolism and translation.

Main Methods:

• Iterative genome-wide screening to identify regulatory factors.
• Analysis of RNA processing pathways including RNase MRP and RNase P.
• Investigation of feedback circuits controlling RNA processing.

Main Results:

• TRNAU1AP and PRPF39 were identified as key regulators of MALAT1 3'-end processing.
• These factors constitute a novel RNase MRP and P control (RMPPc) pathway.
• The RMPPc pathway integrates control over MALAT1, pre-rRNA, and pre-tRNA processing.
• A single control point involving RPP14 regulates both RNase MRP and RNase P.
• A four-pronged feedback circuit stabilizes post-transcriptional processing of over 90% of human cellular RNA.

Conclusions:

• TRNAU1AP and PRPF39 are essential for controlling MALAT1 abundance.
• The RMPPc pathway plays a fundamental role in RNA processing, impacting translation.
• This pathway establishes integrated control over diverse RNA substrates through a conserved mechanism.