Quantitative proteomics reveals that long non-coding RNA MALAT1 interacts with DBC1 to regulate p53 acetylation

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) with diverse cellular roles.
• Understanding MALAT1's molecular mechanisms requires identifying its interacting proteins.

Purpose of the Study:

• To comprehensively identify proteins interacting with MALAT1.
• To elucidate the functional impact of MALAT1-protein interactions on cellular processes, particularly p53 regulation.

Main Methods:

• High-throughput screening combining RNA pull-down and quantitative proteomics.
• Bioinformatics analysis for network construction and gene ontology annotation.
• Experimental validation using RNA pull-down and RNA immunoprecipitation.

Main Results:

• Identified 127 potential MALAT1-interacting proteins, forming a network of 788 connections.
• MALAT1 is implicated in RNA processing, transcription, ribosomal function, protein degradation, and metabolism.
• Validated MALAT1 interaction with depleted in breast cancer 1 (DBC1) and demonstrated its role in modulating SIRT1 activity and p53 deacetylation.

Conclusions:

• MALAT1 regulates p53 activity through a novel lncRNA-protein interaction mechanism.
• MALAT1 binding to DBC1 releases SIRT1, enhancing its deacetylation of p53.
• This process impacts p53 target gene transcription, promoting cell proliferation and inhibiting apoptosis.