CRISPR家族新成员：CRISPR-Cpf1

近年来,基因组编辑技术得到了飞速发展,该技术正在基础生物学研究、医学、生物技术等多个领域引起一场新的变革.Cpf1,作为CRISPR系统的新成员,极大地扩展了基因编辑靶位点的选择范围,同时其介导的多基因编辑具有明显的优势.另外,较短的crRNA序列也使Cpf1更容易产业化.本文将从Cpf1的结构和编辑特点、应用进展、目前面临的问题及展望等方面进行介绍和总结.     

RNA editing

The term RNA editing describes those molecular processes in which the information content is altered in an RNA molecule. To date such changes have been observed in tRNA. rRNA and mRNA molecules of eukaryotes, but not prokaryotes. The demonstration of RNA editing in prokaryotes may only be a matter of time, considering the range of species in which the various RNA editing processes have been found. RNA editing occurs in the nucleus, as well as in mitochondria and plastids, which are thought to have evolved from prokaryotic-like endosymbionts. Most of the RNA editing processes, however, appear to be evolutionarily recent acquisitions that arose independently. The diversity of RNA editing mechanisms includes nucleoside modifications such as C to U and A to I deaminations, as well as non-templated nucleotide additions and insertions. RNA editing in mRNAs effectively alters the amino acid sequence of the encoded protein so that it differs from that predicted by the genomic DNA sequence.     

Role of telomere in endothelial dysfunction in atherosclerosis

PURPOSE OF REVIEW: Telomeres consist of repeats of G-rich sequence at the end of chromosomes. These DNA repeats are synthesized by enzymatic activity associated with an RNA protein complex called telomerase. In most somatic cells, telomerase activity is insufficient, and telomere length decreases with increasing cell division, resulting in an irreversible cell growth arrest, termed cellular senescence. Cellular senescence is associated with an array of phenotypic changes suggestive of aging. Until recently, cellular senescence has largely been studied as an in-vitro phenomenon; however, there is accumulating evidence that indicates a critical role of telomere function in the pathogenesis of human atherosclerosis. This review attempts to summarize recent work in vascular biology that supports the "telomere hypothesis". We discuss the possible relevance of telomere function to vascular aging and the therapeutic potential of telomere manipulation. RECENT FINDINGS: It has been reported that many of the changes in senescent vascular cell behavior are consistent with known changes seen in age-related vascular diseases. Introduction of telomere malfunction has been shown to lead to endothelial dysfunction that promotes atherogenesis, whereas telomere lengthening extends cell lifespan and protects against endothelial dysfunction associated with senescence. Indeed, recent studies have demonstrated that telomere attrition and cellular senescence occur in the blood vessels and are associated with human atherosclerosis. SUMMARY: Recent findings suggest that vascular cell senescence induced by telomere shortening may contribute to atherogenesis and may provide insights into a novel treatment of antisenescence to prevent atherosclerosis.     

Key microRNAs in the biology of breast cancer; emerging evidence in the last decade

microRNAs (miRNAs) are a family of small noncoding RNAs that play a pivotal role in the regulation of main biological and physiological processes, including cell cycle regulation, proliferation, differentiation, apoptosis, stem cell maintenance, and organ development. Dysregulation of these tiny molecules has been related to different human diseases, such as cancer. It has been estimated that more than 50% of these noncoding RNA sequences are placed on fragile sites or cancer-associated genomic regions. After the discovery of the first specific miRNA signatures in breast cancer, many studies focused on the involvement of these small RNAs in the pathophysiology of breast tumors and their possible clinical implications as reliable prognostic biomarkers or as a new therapeutic approach. Therefore, the present review will focus on the recent findings on the involvement of miRNAs in the biology of breast cancer associated with their clinical implications.     

Therapeutic potential of RNA interference against cellular targets of HIV infection

RNA interference is not only very promising in identifying new targets for drug development, siRNA/shRNA themselves may be directly used as therapeutic agents. In inhibiting viral infections by RNA interference, both viral targets and cellular proteins have been evaluated. Most of the early studies in this field had chosen viral targets for RNA interference. However, recent efforts are mainly focusing on cellular proteins for RNA silencing due to the realization that a variety of viral responses substantially minimize siRNA effects. With the application of siRNA approaching, many new cellular targets relevant to HIV infection have been identified. The value of siRNA/shRNA in the treatment of AIDS is largely dependent on better understanding of the biology of HIV replication. Efforts in the identification of cellular processes with the employment of siRNA/shRNA have shed some new lights on our understanding of how HIV infection occurs. Furthermore, the relative specific effects and simplicity of design makes siRNA/shRNA themselves to be favorable drug leads. J. Zhang and Y. O. Wu contributed equally to this article.     

MicroRNAs as oncogenes

MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Originally discovered in Caenorhabditis elegans, this group of tiny RNAs has moved to the forefront of biology. With over 300 miRNA genes identified in the human genome, and a plethora of predicted mRNA targets, it is believed that these small RNAs have a central role in diverse cellular and developmental processes. Concordant with this, aberrant expression of miRNA genes could lead to human disease, including cancer. Although the connection of miRNAs with cancer has been suspected for several years, four recent studies have confirmed the suspicion that miRNAs regulate cell proliferation and apoptosis, and play a role in cancer.