RNA Helicase P82 Regulates Ribosomal DNA Transcription

RNA helicase P82,an 82-kDa protein,is alternative translated at a non-AUG initiator codon(CUG)by DDX17.The former studies found that P82 was involved in many RNA activities such as RNA unwinding reactions,RNA secondary structure rearrangement.Generally,researches on DDX17 refer to a complex including P72 and P82,whereas the differences between P72 and P82 remain to be clarified.Ribosomal DNA(rDNA)transcription process is very important for ribosomal RNA(rRNA).rRNA is a vital component of Ribosome.Ribosome largely determines cell growth through controlling the protein synthesis.Therefore the rDNA transcription plays an indispensable role for cell growth.According to the Oncomine database we found that DDX17 exhibited higher expression in tumor tissues compared to the normal tissues.P82 is much more important to cell growth than P72 in DDX17 which containing P72 and P82 in our study.P82 stable knockdown tumor cells exhibit declined cell growth comparing with the normal cells,and tumor cells stably overexpressed with P82 protein show increased cell growth.We found that P82,as a nucleolus protein,directly interacted with UBF and SirT7,increased UBF-SirT7 binding,and thereby promoted the formation of pre-initiation complex for rDNA transcription.Our results suggest that P82 is beneficial to ribosome production via cooperating with SirT7 and UBF,eventually contributes to rapid growth of tumor cells.Moreover,Actinomycin D(a common antineoplastic)treatments induce P82 released to the nucleus from the nucleolus accompanied with decreased protein level of P82 in tumor cells.Collectivelly,our results prove that P82 is an oncogene and reveal its intrinsic molecular mechanism in promoting tumor cells growth.Meanwhile,the research on P82 provides a potential target for antineoplastic.