Insights from structures of cancer-relevant pre-mRNA splicing factors.
Insights from structures of cancer-relevant pre-mRNA splicing factors.
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DOI：
10.1016/j.gde.2017.10.008
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发表时间：
2018-03
影响因子：
4
通讯作者：
Kielkopf CL
中科院分区：
文献类型：
--
作者：
Kielkopf CL
前体mRNA剪接因子识别初始转录本内的共有信号，并且作为剪接体机器的齿轮，协调前体mRNA区域的切除和重新连接以实现基因表达。大规模测序表明，编码前体mRNA剪接因子的关键基因中的突变在髓系肿瘤中很常见，也发生在多种其他癌症中。这一发现为针对血液系统和其他恶性肿瘤中的前体mRNA剪接弱点提供了新的治疗机会。突变残基通常会改变一部分转录本的3′剪接位点选择。在这篇综述中，我们强调了来自近期3D结构的机制见解，这些见解揭示了准备进行前体mRNA识别的受影响残基。
Pre-mRNA splicing factors recognize consensus signals within preliminary transcripts, and as cogs of the spliceosome machine, orchestrate the excision and rejoining of pre-mRNA regions for gene expression. Large-scale sequencing has demonstrated that mutations in key genes encoding pre-mRNA splicing factors are common among myeloid neoplasms and also occur in a variety of other cancers. This revelation offers new therapeutic opportunities to target pre-mRNA splicing vulnerabilities in hematologic and other malignancies. The mutated residues typically alter 3′ splice site choice for a subset of transcripts. In this review, we highlight mechanistic insights from recent 3D structures that reveal the affected residues poised for pre-mRNA recognition.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
14.9
作者：
Carrocci TJ;Zoerner DM;Paulson JC;Hoskins AA
通讯作者：
Hoskins AA
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
64.8
作者：
Bertram, Karl;Agafonov, Dmitry E.;Luehrmann, Reinhard
通讯作者：
Luehrmann, Reinhard
影响因子：
16
作者：
Anczuków O;Akerman M;Cléry A;Wu J;Shen C;Shirole NH;Raimer A;Sun S;Jensen MA;Hua Y;Allain FH;Krainer AR
通讯作者：
Krainer AR