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...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.展开更多
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 ...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 boundaries.By 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 database.The SDRs-mediated posttranscriptional processing events including cis-and trans-actions were experimentally detected in majority of the predicted candidates.Extensive 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 molecules.In addition,we show that the paired presence of SDR is necessary but not sufficient in SDR-mediated splicing in transient expression and stable transformation systems.We also show prokaryote is incapable of SDR-mediated premRNA splicing.展开更多
基金Supported by The Agreement between FIMA and the "UTE project CIMA"Red Temática de Investigación Cooperativa en Cáncer RD06 00200061 (to Berasain C and ávila MA)Ciberehd (to Prieto J) from Instituto de Salud Carlos Ⅲ,Grants FIS PI070392 and PI070402 from Ministerio de Sanidad y Con-sumo
文摘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.
基金supported by the National Key Basic Research Program (973 program) (No. 2006CB100205)the National Science Fund for Distinguished Young Scholars (No. 30825030)+2 种基金the National Natural Science Foundation of China (No. 30770466, 90717110, 30970260 and 30971752)the Earmarked Fund for Modern Agro-industry Technology Research System (No. nycytx-01)the National High Technology Research and Development Program of China (863 Program) (No. 2007AA10Z100)
文摘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 boundaries.By 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 database.The SDRs-mediated posttranscriptional processing events including cis-and trans-actions were experimentally detected in majority of the predicted candidates.Extensive 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 molecules.In addition,we show that the paired presence of SDR is necessary but not sufficient in SDR-mediated splicing in transient expression and stable transformation systems.We also show prokaryote is incapable of SDR-mediated premRNA splicing.
