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“Proteome Remodeling by DDX3”

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  • 2018-05-29



▶Subject: “Proteome Remodeling by DDX3”

▶Speaker: Sekyung Oh, Ph. D.

▶Place: Life Science Bldg. #104

DDX3X encodes a DEAD-box family RNA helicase (DDX3) commonly mutated in medulloblastoma, a highly aggressive cerebellar tumor affecting children and adolescents. Despite being implicated in  several  facets  of  RNA  metabolism,  the  nature  and  scope  of  DDX3ʹs  interactions  with  RNA remain  unclear.  Here,  I  show  DDX3  collaborates  extensively  with  the  translation  initiation machinery through direct binding to 5ʹUTRs of nearly all coding RNAs, specific sites on the 18S rRNA, and multiple components of the translation initiation complex. Impairment of translation initiation  is  also  evident  in  primary  medulloblastomas  harboring  mutations  in DDX3X,  further highlighting DDX3ʹs role in this process. Arsenite-induced stress shifts DDX3 binding from the 5ʹUTR into the coding region of mRNAs concomitant with a general reduction of translation, and both  the  shift  of  DDX3  on  mRNA  and  decreased  translation  are  blunted  by  expression  of  a catalytically-impaired, medulloblastoma-associated DDX3R534Hvariant. Furthermore, despite the global  repression  of  translation  induced  by  arsenite,  translation  is  preserved  on  select  genes involved  in  chromatin  organization  in  DDX3R534H-expressing  cells.  Thus,  DDX3  interacts extensively  with  RNA  and  ribosomal  machinery  to  help  remodel  the  translation  landscape  in response to stress, while cancer-related DDX3 variants adapt this response to selectively preserve translation.

▶Inquiry: Prof. Joo-Yeon Yoo (279-2346)

*This seminar will be given in Korean.
*Please refrain from taking photos during seminars

790-784 SAN 31, HYOJA-DONG, NAM-GU, POHANG, GYUNGBUK. KOREA 생체분자기능연구사업단 TEL : 054-279-2997

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