Studies On The Modulation Of P53 On Retrotransposition

The retrotransposon LIN E-1 is a kind of elements that can move autonomously in the genome.More than 25% of the human genome is produced by LINE-1's transposon directly or by other non-autonomous transposons with the assistance of reverse transcriptase encoded by LIN E-1.Therefore,LIN E-1 is considered to be the dominant transposon in the human genome.It has been confirmed that LINE-1 induceDNA double-strand breaks and causegenomic instability.It has been demonstrated that more than 100 diseases related to retrotransposition.Multiple defense mechanisms were discovered to regulate LINE-1 mobility in mammalian cells.P53 gene as one of the most important tumor suppressor ge nes has the inhibition ability on LINE-1 retrotransposition.The modulation mechanisms of P53 on LIN E-1 mobility are under investigation.SAMHD1 and APOBECs proteins restrict the LIN E-1 retrotransposition through affecting the function of ORF1 protein and ORF2 protein.Herein,we detected the ability of wild type P53 on LINE-1 restriction,the interaction of P53 protein with LINE-1 RNP and the effects of P53 on the reverse transcriptase activity of ORF2 protein.Our data shown that P53 protein have the inhibitionability on LINE-1 retrotransposion.Mutation P53(R175H,R273 H,G245S,R248 Q,R248W,R249 S,R282W)proteins abort the ability on LIN E-1 restriction.Wild type P53 protein interacts with LINE-1 RNP and further restricts the reverse transcriptase act ivity of ORF2 p.While P53 R273 H loses the ability on LIN E-1 restriction,but maintain the inhibition ability on ORF2 reverse transcriptase,it suggests that some unknown mechanisms are involved in P53 restricting LIN E-1 restrotransposition.Meanwhile we use colon cancer cell line,HC T116,and demonstrated that wild P53 protein can inhibit the expression of endogenous LINE-1 mRNA.This study provides basic experimental evidence for understanding the mechanism of retrotransposon elements regulated by P53.It will open a new insights to explore the retrotransposition-related disease.