Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors

Nonsense-mediated decay is well known by the lucid definition of being a RNA surveillance mechanism that ensures the speedy degradation of mRNAs containing premature translation termination codons. However, as we review here, NMD is far from being a simple quality control mechanism; it also regulates the stability of many wild-type transcripts. We summarise the abundance of research that has characterised each of the NMD factors and present a unified model for the recognition of NMD substrates. The contentious issue of how and where NMD occurs is also discussed, particularly with regard to P-bodies and SMG6-driven endonucleolytic degradation. In recent years, the discovery of additional functions played by several of the NMD factors has further complicated the picture. Therefore, we also review the reported roles of UPF1, SMG1 and SMG6 in other cellular processe

tRNASec is transcribed by RNA polymerase II in Trypanosoma brucei but not in humans

Nuclear-encoded tRNAs are universally transcribed by RNA polymerase III (Pol-III) and contain intragenic promoters. Transcription of vertebrate tRNASec however requires extragenic promoters similar to Pol-III transcribed U6 snRNA. Here, we present a comparative analysis of tRNASec transcription in humans and the parasitic protozoa Trypanosoma brucei, two evolutionary highly diverged eukaryotes. RNAi-mediated ablation of Pol-II and Pol-III as well as oligo-dT induced transcription termination show that the human tRNASec is a Pol-III transcript. In T. brucei protein-coding genes are polycistronically transcribed by Pol-II and processed by trans-splicing and polyadenylation. tRNA genes are generally clustered in between polycistrons. However, the trypanosomal tRNASec genes are embedded within a polycistron. Their transcription is sensitive to α-amanitin and RNAi-mediated ablation of Pol-II, but not of Pol-III. Ectopic expression of the tRNASec outside but not inside a polycistron requires an added external promoter. These experiments demonstrate that trypanosomal tRNASec, in contrast to its human counterpart, is transcribed by Pol-II. Synteny analysis shows that in trypanosomatids the tRNASec gene can be found in two different polycistrons, suggesting that it has evolved twice independently. Moreover, intron-encoded tRNAs are present in a number of eukaryotic genomes indicating that Pol-II transcription of tRNAs may not be restricted to trypanosomatid

Different waves and directions of Neolithic migrations in the Armenian Highland

Background: The peopling of Europe and the nature of the Neolithic agricultural migration as a primary issue in the modern human colonization of the globe is still widely debated. At present, much uncertainty is associated with the reconstruction of the routes of migration for the first farmers from the Near East. In this context, hospitable climatic conditions and the key geographic position of the Armenian Highland suggest that it may have served as a conduit for several waves of expansion of the first agriculturalists from the Near East to Europe and the North Caucasus. Results: Here, we assess Y-chromosomal distribution in six geographically distinct populations of Armenians that roughly represent the extent of historical Armenia. Using the general haplogroup structure and the specific lineages representing putative genetic markers of the Neolithic Revolution, haplogroups R1b1a2, J2, and G, we identify distinct patterns of genetic affinity between the populations of the Armenian Highland and the neighboring ones north and west from this area. Conclusions: Based on the results obtained, we suggest a new insight on the different routes and waves of Neolithic expansion of the first farmers through the Armenian Highland. We detected at least two principle migratory directions: (1) westward alongside the coastline of the Mediterranean Sea and (2) northward to the North Caucasus. Electronic supplementary material The online version of this article (doi:10.1186/s13323-014-0015-6) contains supplementary material, which is available to authorized users

Role of UCP1 gene variants in interethnic differences in the development of cardio-metabolic diseases

Cardio-metabolic diseases (CMDs) comprise a cluster of risk factors that contribute to chronic pathological conditions with adverse consequences for cardiovascular function and metabolic processes. A wide range of CMD prevalence rates among different ethnic groups has been documented. In view of accumulated evidence, there is a trend toward increasing CMD prevalence rates in Eastern Europe and Western Asia. Numerous studies have revealed an association between uncoupling protein 1 (UCP1) gene variants and CMDs. UCP1 activity is essential for brown adipose tissue (BAT)-mediated thermogenesis. Experimental animal studies and epidemiological studies in humans highlight the significance of BAT-mediated thermogenesis in protecting against obesity and maintaining a lean phenotype. We hypothesize that the genetic variation in UCP1 gene expression observed among different ethnic groups could contribute to the ethnic-specific predisposition to CMD development. Constructing such prevalence maps of UCP1 gene variants could contribute significantly into identifying high-risk ethnic groups predisposed to the development of CMDs, and further shaping public health policies by the improvement of existing preventive and management strategies

Molecular detection of prostate specific antigen in patients with prostate cancer or benign prostate hyperplasia the first investigation from Iran

Prostate cancer is the second common form of cancer in men. Detection of circulating Prostate Specific Antigen (PSA) transcripts has effectively been used for early diagnosis of prostate cancer cells. This investigation employed a reverse transcriptase polymerase chain reaction (RT-PCR) technique to distinguish the patients with either localized or metastatic prostate cancer (CaP) vs. Benign Prostate Hyperplasia (BPH) and control subjects, as compared with clinical and pathological records. With reservation of ethical issues, blood samples were collected from 60 cases. Based on pathological and clinical findings, 25 patients (20 with localized cancer, 5 with metastatic), 22 with BPH, and 13 healthy (including 3 females) subjects as negative controls, were selected from Shariati, Mehrad, Sina,, Khatam and Atie Hospitals in Tehran, Iran. RT-PCR for a 260 bp PSA transcript was then performed. Clinical and pathological records were used for the assessment and comparison of PSA RT-PCR results. None of the control subjects and BPH (with 7 exceptions) were found positive by RT-PCR (Relative specificity= 72.7). In patients with prostate cancer, 21 out of 25 were found PSA positive (Relative sensitivity= 83.4) and the remaining 3 have been shown to be PSA negative (Positive predictive value= 83.4). All of 5 metastatic patients (100) revealed PSA positive results. Our data reflects the clinical relevance and significance of RT-PCR results as assessed with clinical and pathological examinations. PSA RT-PCR might be used as a powerful means for diagnosis, even when either pathological or clinical findings are negative, and could be employed for further molecular epidemiology surveys

The First Case of Familial Mediterranean Fever Associated with Renal Amyloidosis in Korea

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by periodic episodes of fever and recurrent polyserositis. It is caused by a dysfunction of pyrin (or marenostrin) as a result of a mutation within the MEFV gene. It occurs mostly in individuals of Mediterranean origin; however, it has also been reported in non-Mediterranean populations. In this report, we describe the first case of FMF in a Korean child. As eight-year-old boy presented recurrent febrile attacks from an unknown cause, an acute scrotum and renal amyloidosis. He also showed splenomegaly, lymphadenopathy, pleural effusion, ascites and elevated acute phase reactants. After MEFV gene analysis, he was diagnosed as FMF combined with amyloidosis

Construction of a Suite of Computable Biological Network Models Focused on Mucociliary Clearance in the Respiratory Tract

Mucociliary clearance (MCC), considered as a collaboration of mucus secreted from goblet cells, the airway surface liquid layer, and the beating of cilia of ciliated cells, is the airways’ defense system against airborne contaminants. Because the process is well described at the molecular level, we gathered the available information into a suite of comprehensive causal biological network (CBN) models. The suite consists of three independent models that represent (1) cilium assembly, (2) ciliary beating, and (3) goblet cell hyperplasia/metaplasia and that were built in the Biological Expression Language, which is both human-readable and computable. The network analysis of highly connected nodes and pathways demonstrated that the relevant biology was captured in the MCC models. We also show the scoring of transcriptomic data onto these network models and demonstrate that the models capture the perturbation in each dataset accurately. This work is a continuation of our approach to use computational biological network models and mathematical algorithms that allow for the interpretation of high-throughput molecular datasets in the context of known biology. The MCC network model suite can be a valuable tool in personalized medicine to further understand heterogeneity and individual drug responses in complex respiratory diseases

Report of the 1st and 2nd Mystery of Reactive Oxygen Species Conferences

Non peer reviewe

tRNASec is transcribed by RNA polymerase II in Trypanosoma brucei but not in humans

Nuclear-encoded tRNAs are universally transcribed by RNA polymerase III (Pol-III) and contain intragenic promoters. Transcription of vertebrate tRNASec however requires extragenic promoters similar to Pol-III transcribed U6 snRNA. Here, we present a comparative analysis of tRNASec transcription in humans and the parasitic protozoa Trypanosoma brucei, two evolutionary highly diverged eukaryotes. RNAi-mediated ablation of Pol-II and Pol-III as well as oligo-dT induced transcription termination show that the human tRNASec is a Pol-III transcript. In T. brucei protein-coding genes are polycistronically transcribed by Pol-II and processed by trans-splicing and polyadenylation. tRNA genes are generally clustered in between polycistrons. However, the trypanosomal tRNASec genes are embedded within a polycistron. Their transcription is sensitive to α-amanitin and RNAi-mediated ablation of Pol-II, but not of Pol-III. Ectopic expression of the tRNASec outside but not inside a polycistron requires an added external promoter. These experiments demonstrate that trypanosomal tRNASec, in contrast to its human counterpart, is transcribed by Pol-II. Synteny analysis shows that in trypanosomatids the tRNASec gene can be found in two different polycistrons, suggesting that it has evolved twice independently. Moreover, intron-encoded tRNAs are present in a number of eukaryotic genomes indicating that Pol-II transcription of tRNAs may not be restricted to trypanosomatids

Azokh caves excavations 2002-2006: Middle-Upper palaeolithic transition in Nagorno-Karabagh

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu