Laboratory for Transcription Structural Biology
- E-mail：shunichi.sekine[at]riken.jpPlease replace [at] with @.
Shedding light on molecular mechanisms underlying biological phenomena
Life activities are supported by numerous biomolecules, which communicate with each other and constitute huge assemblies to fulfill diverse cellular needs. In order to visualize their architecture and elucidate their action mechanisms, our team analyzes their 3D structures by cryo-electron microscopy and X-ray crystallography. Our main focus is on huge complexes such as complexes of RNA polymerase and transcription factors, and we unravel molecular mechanisms behind various important biological phenomena. Furthermore, viral or bacterial proteins involved in replication and/or transcription are one of the major drug targets, and our team provides the structural foundations for the drug discovery research.
Transcription elongation factors Elf1 and Spt4/5 intervene between the transcribing RNA polymerase II and the nucleosome, to facilitate the smooth passage of the polymerase through SHL barriers.
Structures of the nucleosome-transcribing RNA polymerase II. The polymerase progresses through the nucleosome by gradually tearing DNA from histones. It stalls at four locations (SHL –6, –5, –2, and –1), and those structures were solved by cryo-EM.
Cryo-EM density map of the RNA polymerase II elongation complex (left). Structure of the RNA polymerase II elongation complex bound with Spt4, Spt5, Elf1, and TFIIS, elucidated by cryo-EM and Xray crystallography (right).
The structure of RNA polymerase stalled due to incorporation of a mismatched nucleotide (left) and that bound with a transcription factor that stimulates proofreading of the mismatch (right).
- Structural bases of transcription and its-related phenomena
- Advancement of technologies for the structural analyses of supramolecular complexes
- Structural basis of viral and bacterial replication/transcription toward drug discovery
Main Publications List
- Ehara H, Kujirai T, Fujino Y, et.al.
Structural insight into nucleosome transcription by RNA polymerase II with elongation factors.
Science 363(6428). 744-747 (2019) doi: 10.1126/science.aav8912
- Kujirai T, Ehara H, Fujino Y, et al.
Structural basis of the nucleosome transition during RNA polymerase II passage.
Science 362(6414). 595-598 (2018) doi: 10.1126/science.aau9904
- Ooi WY, Murayama Y, Mekler V, et al.
A Thermus phage protein inhibits host RNA polymerase by preventing template DNA strand loading during open promoter complex formation.
Nucleic Acids Research 46(1). 431-441 (2017) doi: 10.1093/nar/gkx1162
- Ehara H, Yokoyama T, Shigematsu H, et al.
Structure of the complete elongation complex of RNA polymerase II with basal factors.
Science 357(6354), 921-924 (2017) doi: 10.1126/science.aan8552
- Ehara H, Umehara T, Sekine S, et al.
Crystal structure of RNA polymerase II from Komagataella pastoris.
Biochemical and Biophysical Research Communications 487(2), 230-235 (2017). doi:10.1016/j.bbrc.2017.04.039
- Shimizu H, Miyazaki H, Ohsawa N, et al.
Structure-based site-directed photo-crosslinking analyses of multimeric cell-adhesive interactions of voltage-gated sodium channel β subunits.
Scientific Reports 6, 26618 (2016) doi: 10.1038/srep26618
- Sekine S, Murayama Y, Svetlov V, et al.
Ratcheting of RNA polymerase toward structural principles of RNA polymerase operations.
Transcription 6(3). 56-60 (2015). doi: 10.1080/21541264.2015.1059922
- Sekine S, Murayama Y, Svetlov V, et al.
The ratcheted and ratchetable structural states of RNA polymerase underlie multiple transcriptional functions.
Molecular Cell 57(3). 408-421 (2015) doi: 10.1016/j.molcel.2014.12.014
- Naganuma M, Sekine S, Chong YE, et al.
The selective tRNA aminoacylation mechanism based on a single G•U pair.
Nature 510(7506). 507-511 (2014) doi: 10.1038/nature13440
- Tagami S, Sekine S, Minakhin L, et al.
Structural basis for promoter specificity switching of RNA polymerase by a phage factor
Genes & Development 28(5). 521-531 (2014) doi: 10.1101/gad.233916.113
- Itoh Y, Brocker MJ, Sekine S, et al.
Decameric SelA•tRNASec Ring Structure Reveals Mechanism of Bacterial Selenocysteine Formation.
Science 340(6128). 75-78 (2013) doi: 10.1126/science.1229521
- Tagami S, Sekine S, Kumarevel T, et al.
Crystal structure of bacterial RNA polymerase bound with a transcription inhibitor protein.
Nature 468(7326). 978-982 (2010) doi:10.1038/nature09573
|Shun-ichi SekineTeam Leader||shunichi.sekine[at]riken.jp||CV|
|Kumarevel ThirumananseriSenior Research Scientist|
|Haruhiko EharaResearch Scientist|
|Yuko MurayamaResearch Scientist|
|Takuo OsawaResearch Scientist|
|Mari AokiTechnical Staff I|
*：concurrent / Please replace [at] with @.