MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

http://bartellab.wi.mit.edu/publication_reprints/Bartel_Cell09.pdf

MicroRNAs: Target Recognition and Regulatory Functions

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.

/pdf/signatures-of-mutational-processes-in-human-cancer-j3duru54oq.pdf

Signatures of mutational processes in human cancer

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. The two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events. Since then, hundreds of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. MicroRNAs have diverse expression patterns and might regulate various developmental and physiological processes. Their discovery adds a new dimension to our understanding of complex gene regulatory networks.

/pdf/micrornas-small-rnas-with-a-big-role-in-gene-regulation-3a05xihg95.pdf

MicroRNAs: small RNAs with a big role in gene regulation

The purpose of this study was to investigate the developmental change of epithelial Na + channel function in epithelial cells of rat Reissner's membrane. The Reissner's membrane was isolated from the upper turn of the cochlea at different stages of development. The vibrating probe technique was chosen to measure transepithelial currents under short circuit conditions. Amiloride-sensitive Na + current in the Reissner's membrane developed postnatally between days 3 and 5, which was completely blocked by amiloride. This tendency remained from days 5 through 14. Development of Na + transport in epithelial cells of the Reissner's membrane may contribute considerably to the accomplishment of low Na + concentration in the endolymph during early neonatal period.

Developmental change of Na(+)-absorptive function in Reissner's membrane epithelia.

The adaptor protein (AP) complexes are involved in membrane transport of many proteins. There are 3 AP complexes in C. elegans unlike mammals that have four. To study the biological functions of the AP-3 complexes of C. elegans, we sought homologues of the mouse and human genes that encode subunits of the AP-3 complexes by screening C. elegans genomic and EST sequences. We identified single copies of homologues of the m3, s3, b3 and d genes. The medium chain of AP-3 is encoded by a single gene in C. elegans but two different genes in mammals. Since there are no known mutations in these genes in C. elegans, we performed RNAi to assess their functions in development. RNAi of each of the genes caused embryonic and larval lethal phenotypes. APM-3 is expressed in most cells, particularly strongly in spermatheca and vulva. We conclude that the products of the C. elegans m3, s3, b3 and d genes are essential for embryogenesis and larval development.

The AP-3 clathrin-associated complex is essential for embryonic and larval development in Caenorhabditis elegans.

ObjectiveTo evaluate the efficacy of tinnitus retraining therapy (TRT), especially in patients who did not revisit the clinic after starting the program, and to determine the current status of patients who were lost to follow-up.Study DesignTelephone survey.SettingTertiary referral center.PatientsFo

Assessing the effects of tinnitus retraining therapy in patients lost to follow-up: a telephone survey.

Mice lacking IκB-ζ, a protein encoded by the Nfkbiz gene, spontaneously develop a Sjogren's syndrome-like disease involving the lachrymal glands, but no salivary gland symptoms have been reported. We found that Nfkbiz-/- female mice presented a significantly reduced salivary flow rate, focal lymphocytic sialadenitis (FLS), and a dysbiotic oral microbiota at week 24. To dissect the contributions of genetic and environmental factors to the salivary gland phenotype, Nfkbiz+/+ and Nfkbiz-/- mice were cohoused after weaning and evaluated at week 20. Cohousing alleviated the salivary gland phenotype of Nfkbiz-/- mice but did not induce any disease phenotype in Nfkbiz+/+ mice. Additionally, the oral microbiota in the cohoused mice was synchronized toward that in Nfkbiz+/+ mice. In conclusion, IκB-ζ-deficient mice developed hyposalivation and FLS, in which a dysbiotic oral microbiota played an important role. This finding suggests that the dysbiotic oral microbiota could be a therapeutic target.

/pdf/association-of-a-dysbiotic-oral-microbiota-with-the-d4bbd8d2cw.pdf

Association of a dysbiotic oral microbiota with the development of focal lymphocytic sialadenitis in IκB-ζ-deficient mice.

Guidance molecules, receptors, and downstream signaling pathways involved in the asymmetric neuronal cell migration and process outgrowth have been identified from genetic studies using model organisms, most of which are evolutionarily conserved. In the nematode Caenorhabditis elegans, the roles of Wnt ligands and their receptors in the polarization of specific sets of neurons along the anterior-posterior (A-P) body axis have been well elucidated, but their downstream effectors are relatively unknown. Here, we report yap-1, encoding an evolutionarily conserved transcriptional co-activator, as a novel player in the Wnt-mediated asymmetric development of specific neurons in C. elegans. We found that the loss of yap-1 activity failed to restrict the dendritic extension of ALM neurons to the anterior orientation, which is similar to the phenotype caused by defective cwn-1 and cwn-2 Wnt gene activities. Cell-specific rescue experiments showed that yap-1 acts in the cell autonomous manner to polarize ALM dendrites. We also found that subcellular localization of YAP-1 was spatio-temporally regulated. The loss of yap-1 in Wnt-deficient mutants did not increase the severity of the ALM polarity defect of the mutants. Wnt-deficient animals displayed abnormal subcellular localization of YAP-1 in touch receptor neurons, suggesting that yap-1 may act downstream of the cwn-1/cwn-2 Wnt ligands for the ALM polarization process. Together, we have identified a new role for YAP-1 in neuronal development and our works will contribute to further understanding of intracellular events in neuronal polarization during animal development.

Junho Lee

Papers

Developmental change of Na(+)-absorptive function in Reissner's membrane epithelia.

The AP-3 clathrin-associated complex is essential for embryonic and larval development in Caenorhabditis elegans.

Assessing the effects of tinnitus retraining therapy in patients lost to follow-up: a telephone survey.

Association of a dysbiotic oral microbiota with the development of focal lymphocytic sialadenitis in IκB-ζ-deficient mice.

Involvement of YAP-1, the Homolog of Yes-Associated Protein, in the Wnt-Mediated Neuronal Polarization in Caenorhabditis elegans.