Home
Resources
Publications
The PRMT5/WDR77 Complex Regulates Alternative Splicing Through ZNF326 in Breast Cancer

The PRMT5/WDR77 Complex Regulates Alternative Splicing Through ZNF326 in Breast Cancer

Madhumitha Rengasamy, Fan Zhang, Ajay Vashisht, Won-Min Song, Francesca Aguilo, Yifei Sun, SiDe Li, Weijia Zhang, Bin Zhang, James A Wohlschlegel, Martin J Walsh

Nucleic Acids Res. 2017 Nov 2;45(19):11106-11120.

PMID: 28977470

Abstract:

We observed overexpression and increased intra-nuclear accumulation of the PRMT5/WDR77 in breast cancer cell lines relative to immortalized breast epithelial cells. Utilizing mass spectrometry and biochemistry approaches we identified the Zn-finger protein ZNF326, as a novel interaction partner and substrate of the nuclear PRMT5/WDR77 complex. ZNF326 is symmetrically dimethylated at arginine 175 (R175) and this modification is lost in a PRMT5 and WDR77-dependent manner. Loss of PRMT5 or WDR77 in MDA-MB-231 cells leads to defects in alternative splicing, including inclusion of A-T rich exons in target genes, a phenomenon that has previously been observed upon loss of ZNF326. We observed that the alternatively spliced transcripts of a subset of these genes, involved in proliferation and tumor cell migration like REPIN1/AP4, ST3GAL6, TRNAU1AP and PFKM are degraded upon loss of PRMT5. In summary, we have identified a novel mechanism through which the PRMT5/WDR77 complex maintains the balance between splicing and mRNA stability through methylation of ZNF326.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR424854	SOLu-Trypsin Dimethylated			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: