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MALAT1 downregulation is associated with polycystic ovary syndrome via binding with MDM2 and repressing P53

Yan Li1, Yungai Xiang1, Yuxia Song1

  • 1Reproductive Center, The Second Affiliated Hospital of Zhengzhou University, 450014, No. 2 Jingba Road, Zhengzhou, Henan, China.

Molecular and Cellular Endocrinology
|December 9, 2021
PubMed

Insights

Polycystic ovary syndrome (PCOS) involves the long non-coding RNA MALAT1 interacting with proteins MDM2 and PARP1. MALAT1 knockdown in granulosa cells impacts p53 levels, affecting cell apoptosis and proliferation in PCOS.

Area of Science:

  • Reproductive biology
  • Molecular genetics
  • Cellular mechanisms

Background:

  • Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-aged women, characterized by metabolic and reproductive dysfunction.
  • Long non-coding RNAs, such as MALAT1, are implicated in PCOS pathogenesis.
  • The binding proteins of MALAT1 in human granulosa cells (GCs) remain unidentified, hindering understanding of its role.

Purpose of the Study:

  • To identify MALAT1 binding proteins in primary GCs.
  • To elucidate the functional role of MALAT1-protein interactions in GCs.
  • To investigate the impact of MALAT1 on p53 regulation and granulosa cell function.

Main Methods:

  • RNA antisense purification (RAP) assay coupled with mass spectrometry to identify MALAT1 binding proteins.
  • PAR-CLIP assay and immunofluorescence to confirm MALAT1-protein interactions.
  • Functional studies in KGN cells and primary GCs involving MALAT1 knockdown.

Main Results:

  • MALAT1 was found to interact with MDM2 and PARP1 within the nucleus of GCs.
  • MDM2 binds to the ENE domain of MALAT1 via its ring finger domain.
  • MALAT1 knockdown increased p53 protein levels by inhibiting p53 ubiquitination and degradation, and promoted p53-MDM2 binding, enhancing p53 proteasomal degradation.

Conclusions:

  • MALAT1 plays a regulatory role in GCs by interacting with MDM2 and PARP1.
  • MALAT1 influences p53 stability and degradation pathways.
  • MALAT1 knockdown leads to increased apoptosis and reduced proliferation in GCs, suggesting a role in PCOS pathophysiology.
Keywords:
MALAT1Non-coding RNAPolycystic ovary syndromeUbiquitination

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