Studies on the p90RSK-UBR5 pathway in miRNA-mediated gene silencing = miRNA에 의한 유전자 발현 조절과정에서 p90RSK-UBR5 경로에 대한 연구

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MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate gene expression. For example, miRNAs repress gene expression by recruiting the miRNA-Induced Silencing Complex (miRISC), a ribonucleoprotein complex that contains miRNA-engaged Argonaute (Ago) and the scaffold protein GW182. Recently, ubiquitin-protein ligase E3 component N-recognin 5 (UBR5) has been identified as a component of miRISC. UBR5 directly interact with GW182 proteins and participates in miRNA silencing by recruiting downstream effectors, such as the translation regulator DEAD-box helicase 6 (DDX6) and transducer of ERBB2,1/2,2 (Tob1/2), to the Ago-GW182 complex. However, the regulation of miRISC-associated UBR5 remains largely elusive. In the present study, I showed that UBR5 down-regulates the level of TNF receptor associated factor 3 (TRAF3), a key component of Toll-like receptor signaling, via the miRNA pathway. I further demonstrated that p90 Ribosomal S6 Kinase (p90RSK) is an upstream regulator of UBR5. p90RSK phosphorylates UBR5 at Thr637, Ser1227, and Ser2483, and this phosphorylation is required for the translational repression of TRAF3 mRNA. Phosphorylated UBR5 co-localized with GW182 and Ago2 in cytoplasmic speckles, which implies that miRISC is affected by phospho-UBR5. Collectively, these results indicated that the p90RSK-UBR5 pathway stimulates miRNA-mediated translational repression of TRAF3. My work has added another layer to the regulation of miRISC.
Advisors
Seo, Yeon-Sooresearcher서연수researcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2017
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2017.8,[vi, 84 p. :]

Keywords

UBR5▼amiRNA▼ap90RSK▼aphosphorylation▼aTRAF3▼aArgonaute▼apost-translational modification▼atoll-like receptor; UBR5▼a마이크로 RNA▼ap90RSK▼a인산화▼aTRAF3▼aArgonaute▼a번역 후 변형▼aTLR

URI
http://hdl.handle.net/10203/241861
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=718835&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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