Alternative splicing, RNA-seq and drug discovery

被引:62
作者
Zhao, Shanrong [1 ]
机构
[1] Pfizer Worldwide Res & Dev, Cambridge, MA 02139 USA
关键词
MESSENGER-RNA; PROSTATE-CANCER; RESISTANCE; ISOFORM; TRANSCRIPTION; EXPRESSION; PROTEIN; POLYADENYLATION; QUANTIFICATION; INHIBITION;
D O I
10.1016/j.drudis.2019.03.030
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Alternative splicing, hereafter referred to as AS, is an essential component of gene expression regulation that contributes to the diversity of proteomes. Recent developments in RNA sequencing (RNA-seq) technologies, combined with the advent of computational tools, have enabled transcriptome-wide studies of AS at an unprecedented scale and resolution. RNA mis-splicing can cause human disease, and to target alternative splicing has led to the development of novel therapeutics. Splice variants diversify the repertoire of biomarkers and functionally contribute to drug resistance. Our expanding knowledge of AS variation in human populations holds great promise for improving disease diagnoses and ultimately patient care in the era of sequencing and precision medicine.
引用
收藏
页码:1258 / 1267
页数:10
相关论文
共 93 条
  • [1] Alternative splicing of Bcl-2-related genes: functional consequences and potential therapeutic applications
    Akgul, C
    Moulding, DA
    Edwards, SW
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2004, 61 (17) : 2189 - 2199
  • [2] p53 directly transactivates Δ133p53α, regulating cell fate outcome in response to DNA damage
    Aoubala, M.
    Murray-Zmijewski, F.
    Khoury, M. P.
    Fernandes, K.
    Perrier, S.
    Bernard, H.
    Prats, A-C
    Lane, D. P.
    Bourdon, J-C
    [J]. CELL DEATH AND DIFFERENTIATION, 2011, 18 (02) : 248 - 258
  • [3] Regulation of gene expression by alternative promoters
    Ayoubi, TAY
    VanDeVen, WJM
    [J]. FASEB JOURNAL, 1996, 10 (04) : 453 - 460
  • [4] VEGF gene alternative splicing: pro- and anti-angiogenic isoforms in cancer
    Biselli-Chicote, P. M.
    Oliveira, A. R. C. P.
    Pavarino, E. C.
    Goloni-Bertollo, E. M.
    [J]. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2012, 138 (03) : 363 - 370
  • [5] Near-optimal probabilistic RNA-seq quantification (vol 34, pg 525, 2016)
    Bray, Nicolas L.
    Pimentel, Harold
    Melsted, Pall
    Pachter, Lior
    [J]. NATURE BIOTECHNOLOGY, 2016, 34 (08) : 888 - 888
  • [6] Translating RNA sequencing into clinical diagnostics: opportunities and challenges
    Byron, Sara A.
    Van Keuren-Jensen, Kendall R.
    Engelthaler, David M.
    Carpten, John D.
    Craig, David W.
    [J]. NATURE REVIEWS GENETICS, 2016, 17 (05) : 257 - 271
  • [7] Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines
    Castle, John C.
    Zhang, Chaolin
    Shah, Jyoti K.
    Kulkarni, Amit V.
    Kalsotra, Auinash
    Cooper, Thomas A.
    Johnson, Jason M.
    [J]. NATURE GENETICS, 2008, 40 (12) : 1416 - 1425
  • [8] Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
    Chen, Mo
    Manley, James L.
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (11) : 741 - 754
  • [9] AMAZING SEQUENCE ARRANGEMENT AT 5' ENDS OF ADENOVIRUS-2 MESSENGER-RNA
    CHOW, LT
    GELINAS, RE
    BROKER, TR
    ROBERTS, RJ
    [J]. CELL, 1977, 12 (01) : 1 - 8
  • [10] Function, clinical application, and strategies of Pre-mRNA splicing in cancer
    Di, Cuixia
    Syafrizayanti
    Zhang, Qianjing
    Chen, Yuhong
    Wang, Yupei
    Zhang, Xuetian
    Liu, Yang
    Sun, Chao
    Zhang, Hong
    Hoheisel, Jorg D.
    [J]. CELL DEATH AND DIFFERENTIATION, 2019, 26 (07) : 1181 - 1194