http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
- 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
- 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
RISS 인기검색어
- 검색키워드
- 저자 : Simanshu, Dhirendra K (검색결과 4 건)
- 무료
- 기관 내 무료
- 유료
-
A Phosphate-Binding Pocket within the Platform-PAZ-Connector Helix Cassette of Human Dicer
Tian, Y.,Simanshu, Dhirendra K.,Ma, J.B.,Park, J.E.,Heo, I.,Kim, V.,Patel, Dinshaw J. Cell Press 2014 Molecular cell Vol.53 No.4
We have solved two families of crystal structures of the human Dicer ''platform-PAZ-connector helix'' cassette in complex with small interfering RNAs (siRNAs). The structures possess two adjacently positioned pockets: a 2 nt 3'-overhang-binding pocket within the PAZ domain (3' pocket) and a phosphate-binding pocket within the platform domain (phosphate pocket). One family of complexes contains a knob-like α-helical protrusion, designated ''hDicer-specific helix,'' that separates the two pockets and orients the bound siRNA away from the surface of Dicer, which could be indicative of a product release/transfer state. In the second complex, the helical protrusion is melted/disordered and the bound siRNA is aligned toward the surface of Dicer, suggestive of a cleavage-competent state. These structures allow us to propose that the transition from the cleavage-competent to the postulated product release/transfer state may involve release of the 5'-phosphate from the phosphate pocket while retaining the 3' overhang in the 3' pocket.
-
Dicer recognizes the 5' end of RNA for efficient and accurate processing
Park, Jong-Eun,Heo, Inha,Tian, Yuan,Simanshu, Dhirendra K.,Chang, Hyeshik,Jee, David,Patel, Dinshaw J.,Kim, V. Narry Nature Publishing Group, a division of Macmillan P 2011 Nature Vol.475 No.7355
A hallmark of RNA silencing is a class of approximately 22-nucleotide RNAs that are processed from double-stranded RNA precursors by Dicer. Accurate processing by Dicer is crucial for the functionality of microRNAs (miRNAs). The current model posits that Dicer selects cleavage sites by measuring a set distance from the 3′ overhang of the double-stranded RNA terminus. Here we report that human Dicer anchors not only the 3′ end but also the 5′ end, with the cleavage site determined mainly by the distance (~ 2 nucleotides) from the 5′ end (5′ counting rule). This cleavage requires a 5′ terminal phosphate group. Further, we identify a novel basic motif (5′ pocket) in human Dicer that recognizes the 5′ -phosphorylated end. The 5′ counting rule and the 5′ anchoring residues are conserved in Drosophila Dicer-1, but not in Giardia Dicer. Mutations in the 5′ pocket reduce processing efficiency and alter cleavage sites in vitro. Consistently, miRNA biogenesis is perturbed in vivo when Dicer-null embryonic stem cells are replenished with the 5′ pocket mutant. Thus, 5′-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs.
-
TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms
Kim, Boseon,Ha, Minju,Loeff, Luuk,Chang, Hyeshik,Simanshu, Dhirendra K,Li, Sisi,Fareh, Mohamed,Patel, Dinshaw J,Joo, Chirlmin,Kim, V Narry John WileySons, Ltd 2015 The EMBO journal Vol.34 No.13
<P>Terminal uridylyl transferases (TUTs) function as integral regulators of microRNA (miRNA) biogenesis. Using biochemistry, single-molecule, and deep sequencing techniques, we here investigate the mechanism by which human TUT7 (also known as ZCCHC6) recognizes and uridylates precursor miRNAs (pre-miRNAs) in the absence of Lin28. We find that the overhang of a pre-miRNA is the key structural element that is recognized by TUT7 and its paralogues, TUT4 (ZCCHC11) and TUT2 (GLD2/PAPD4). For group II pre-miRNAs, which have a 1-nt 3′ overhang, TUT7 restores the canonical end structure (2-nt 3′ overhang) through mono-uridylation, thereby promoting miRNA biogenesis. For pre-miRNAs where the 3′ end is further recessed into the stem (as in 3′ trimmed pre-miRNAs), TUT7 generates an oligo-U tail that leads to degradation. In contrast to Lin28-stimulated oligo-uridylation, which is processive, a distributive mode is employed by TUT7 for both mono- and oligo-uridylation in the absence of Lin28. The overhang length dictates the frequency (but not duration) of the TUT7-RNA interaction, thus explaining how TUT7 differentiates pre-miRNA species with different overhangs. Our study reveals dual roles and mechanisms of uridylation in repair and removal of defective pre-miRNAs.</P>
-
Uridylation by TUT4 and TUT7 Marks mRNA for Degradation
Lim, Jaechul,Ha, Minju,Chang, Hyeshik,Kwon, S.?Chul,Simanshu, Dhirendra?K.,Patel, Dinshaw?J.,Kim, V.?Narry Elsevier 2014 Cell Vol.159 No.6
<P><B>Summary</B></P> <P>Uridylation occurs pervasively on mRNAs, yet its mechanism and significance remain unknown. By applying TAIL-seq, we identify TUT4 and TUT7 (TUT4/7), also known as ZCCHC11 and ZCCHC6, respectively, as mRNA uridylation enzymes. Uridylation readily occurs on deadenylated mRNAs in cells. Consistently, purified TUT4/7 selectively recognize and uridylate RNAs with short A-tails (less than ∼25?nt) in?vitro. PABPC1 antagonizes uridylation of polyadenylated mRNAs, contributing to the specificity for short A-tails. In cells depleted of TUT4/7, the vast majority of mRNAs lose the oligo-U-tails, and their half-lives are extended. Suppression of mRNA decay factors leads to the accumulation of oligo-uridylated mRNAs. In line with this, microRNA induces uridylation of its targets, and TUT4/7 are required for enhanced decay of microRNA targets. Our study explains the mechanism underlying selective uridylation of deadenylated mRNAs and demonstrates a fundamental role of oligo-U-tail as a molecular mark for global mRNA decay.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TUT4 and TUT7 uridylate mRNAs and thereby facilitate mRNA decay </LI> <LI> TUT4 and TUT7 selectively uridylate deadenylated mRNAs with a short A-tail (<∼25 nt) </LI> <LI> Uridylation is induced by miRNAs and enhances degradation of miRNA targets </LI> <LI> Oligo-U-tail serves as a general molecular mark for mRNA decay </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
연관 검색어 추천
이 검색어로 많이 본 자료
활용도 높은 자료
