Page 128 - ebook

[A. Biochemistry/Molecular Biology] A-64

Decreased SRSF7 mediates MDM2 variant generation in

cellular senescence

Jiwon Hong¹,²,³, Seongki Min¹,²,³, Gyesoon Yoon¹,²,³, Su Bin Lim¹,²,³*

¹Department of Biochemistry & Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea,

²Inflamm-aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea, ³Department

of Biomedical Science, The Graduate School, Ajou University, Suwon 16499, Korea

Cellular senescence is a state of irreversible cellular growth arrest, which contributes to organismal aging and aging-
associated diseases. Several molecular causes are defined and the change in splicing pattern has been recently

reported as an emerging contributor to cellular senescence. In our previous study, deregulation of several
spliceosomal genes was involved in replicative senescence and splicing variants of MDM2 were formed during

senescence. However, it is still unclear how spliceosomal genes are individually involved in cellular senescence.
Among those genes, we focused on serine and arginine rich splicing factor 7 (SRSF7) and investigated whether

SRSF7 played a key role in the alternative splicing of MDM2. During cellular senescence, mRNA and protein level
of SRSF7 clearly decreased. Interestingly, when SRSF7 was suppressed, cellular senescence was induced and several

MDM2 variants were newly generated. We found a potential variant through RNA-seq analysis and confirmed the
formation of it in the absence of SRSF7. The variant lacks p53 binding domain, suggesting that it is unable to

degrade p53. These results indicate that SRSF7 plays an important role in the alternative splicing of MDM2 and its
depletion triggers p53-mediated cellular senescence, implying its proper regulation is essential to prevent the entry
into cellular senescence.