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Impairment of pre-mRNA splicing in liver disease: Mechanisms and consequences

World Journal of Gastroenterology 2010年第25期16卷 3091-3102页

作者： Carmen Berasain Saioa Gońi Josefa Castillo Maria Ujue Latasa Jesús Prieto Matias A Avila Division of Hepatologyand Gene Therapy CIMA University of Navarra Pamplona31008 Spain

Pre-mRNA splicing is an essential step in the process of gene expression in eukaryotes and consists of the removal ofintrons and the linking of exons to generate mature mRNAs. This is a highly regulated mechanism that allows the alternative usage of exons, the retention ofintronic sequences and the generation of exonic sequences of variable length. Most human genes undergo splicing events, and disruptions of this process have been associated with a variety of diseases, including cancer. Hepatocellular carcinoma (HCC) is a molecularly heterogeneous type of tumor that usually develops in a cirrhotic liver. Alterations in pre-mRNA splicing of some genes have been observed in liver cancer, and although still scarce, the available data suggest that splicing defects may have a role in hepatocarcinogenesis. Here we briefly review the general mechanisms that regulatepre-mRNA splicing, and discuss some examples that illustrate how this process is impaired in liver tumorigenesis, and may contribute to HCC development. We believe that a more thorough examination of pre-mRNA splicing is still needed to accurately draw the molecular portrait of liver cancer. This will surely contribute to a better understanding of the disease and to the development of new effective therapies.

关键词： Cell signalling Hepatocarcinogenesis premrna splicing splicing factors Targeted anticancer therapy

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A conserved unusual posttranscriptional processing mediated by short,direct repeated (SDR) sequences in plants

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Journal of Genetics and Genomics 2010年第1期37卷 85-99页

作者： Xiangli Niu Di Luo Shaopei Gao Guangjun Ren Lijuan Chang Yuke Zhou Xiaoli Luo Yuxiang Li Pei Hou Wei Tang Bao-Rong Lu Yongsheng Liu College of Agricultural and Life Sciences Chongqing UniversityChongqing 400030China Ministry of Education Key Laboratory for Bio-resource and Eco-environment College of Life Science and State Key Laboratory of BiotherapySichuan UniversityChengdu 610064China c Institute of Crop Research Sichuan Academy of Agricultural SciencesChengdu 610066China Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering Institute of Biodiversity ScienceFudan UniversityShanghai 200433China1

In several stress responsive gene loci of monocot cereal crops,we have previously identified an unusual posttranscriptional processing mediated by paired presence of short direct repeated （SDR） sequences at 5＇ and 3＇ splicing junctions that are distinct from conventional （U2/U12-type） splicing *** using the known SDR-containing sequences as probes,24 plant candidate genes involved in diverse functional pathways from both monocots and dicots that potentially possess SDR-mediated posttranscriptional processing were predicted in the GenBank *** SDRs-mediated posttranscriptional processing events including cis-and trans-actions were experimentally detected in majority of the predicted *** sequence analysis demonstrates several types of SDR-associated splicing peculiarities including partial exon deletion,exon fragment repetition,exon fragment scrambling and trans-splicing that result in either loss of partial exon or unusual exonic sequence rearrangements within or between RNA *** addition,we show that the paired presence of SDR is necessary but not sufficient in SDR-mediated splicing in transient expression and stable transformation *** also show prokaryote is incapable of SDR-mediated premrna splicing.

关键词： posttranscriptional processing short direct repeat (SDR) premrna splicing plant

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