microRNA-Mediated Messenger RNA Deadenylation Contributes to Translational Repression in Mammalian Cells

Animal microRNAs (miRNAs) typically regulate gene expression by binding to partially complementary target sites in the 3′ untranslated region (UTR) of messenger RNA (mRNA) reducing its translation and stability. They also commonly induce shortening of the mRNA 3′ poly(A) tail, which contributes to their mRNA decay promoting function. The relationship between miRNA-mediated deadenylation and translational repression has been less clear. Using transfection of reporter constructs carrying three imperfectly matching let-7 target sites in the 3′ UTR into mammalian cells we observe rapid target mRNA deadenylation that precedes measureable translational repression by endogenous let-7 miRNA. Depleting cells of the argonaute co-factors RCK or TNRC6A can impair let-7-mediated repression despite ongoing mRNA deadenylation, indicating that deadenylation alone is not sufficient to effect full repression. Nevertheless, the magnitude of translational repression by let-7 is diminished when the target reporter lacks a poly(A) tail. Employing an antisense strategy to block deadenylation of target mRNA with poly(A) tail also partially impairs translational repression. On the one hand, these experiments confirm that tail removal by deadenylation is not strictly required for translational repression. On the other hand they show directly that deadenylation can augment miRNA-mediated translational repression in mammalian cells beyond stimulating mRNA decay. Taken together with published work, these results suggest a dual role of deadenylation in miRNA function: it contributes to translational repression as well as mRNA decay and is thus critically involved in establishing the quantitatively appropriate physiological response to miRNAs

Involvement of microRNAs in physiological and pathological processes in the lung

To date, at least 900 different microRNA (miRNA) genes have been discovered in the human genome. These short, single-stranded RNA molecules originate from larger precursor molecules that fold to produce hairpin structures, which are subsequently processed by ribonucleases Drosha/Pasha and Dicer to form mature miRNAs. MiRNAs play role in the posttranscriptional regulation of about one third of human genes, mainly via degradation of target mRNAs. Whereas the target mRNAs are often involved in the regulation of diverse physiological processes ranging from developmental timing to apoptosis, miRNAs have a strong potential to regulate fundamental biological processes also in the lung compartment. However, the knowledge of the role of miRNAs in physiological and pathological conditions in the lung is still limited. This review, therefore, summarizes current knowledge of the mechanism, function of miRNAs and their contribution to lung development and homeostasis. Besides the involvement of miRNAs in pulmonary physiological conditions, there is evidence that abnormal miRNA expression may lead to pathological processes and development of various pulmonary diseases. Next, the review describes current state-of-art on the miRNA expression profiles in smoking-related diseases including lung cancerogenesis, in immune system mediated pulmonary diseases and fibrotic processes in the lung. From the current research it is evident that miRNAs may play role in the posttranscriptional regulation of key genes in human pulmonary diseases. Further studies are, therefore, necessary to explore miRNA expression profiles and their association with target mRNAs in human pulmonary diseases

The GridKa Tape Storage: various performance test results and current improvements

Data growth over several years within HEP experiments requires a wider use of storage systems for WLCG Tiered Centers. It also increases the complexity of storage systems, which includes the expansion of hardware components and thereby complicates existing software products more. To cope with such systems is a non-trivial task and requires highly qualified specialists. Storing petabytes of data on tape storage is a still the most cost-effective way. Year after year, the use of a tape storage increases, consequently a detailed study of its optimal use and verification of performance is a key aspect for such a system. It includes several factors, such as performing various performance tests, identifying and eliminating bottlenecks, properly adjusting and improving the current GridKa setup, etc. At present, GridKa uses dCache as the storage system in frontend and TSM as the tape storage backend. dCache provides a plugin interface for exchanging data between dcache and tape. TSS is a TSM-based client developed by the GridKa team. TSS has been in production for over 10 years. The interaction between the GridKa dCache instance and TSM is accomplished using additional scripts that can be further optimized to improve the overall performance of the tape storage. This contribution provides detailed information on the results of various performance tests performed on the GridKa tape and significant improvements of our tape storage performance

The GridKa Tape System: status and outlook

Tape storage is still a cost effective way to keep large amounts of data over a long period of time and it is expected that this will continue in the future. The GridKa tape environment is a complex system of many hardware components and software layers. Configuring this system for optimal performance for all use cases is a non-trivial task and requires a lot of experience. We present the current status of the GridKa tape environment, report on recent upgrades and improvements and plans to further develop and enhance the system, especially with regard to the future requirements of the HEP experiments and their large data centers. The short-term planning mainly includes the transition from TSM to HPSS as the backend and the effects on the connection of dCache and xrootd. Recent changes of the vendor situation of certain tape technologies require a precise analysis of the impact and eventual adaptation of the mid-term planning, in particular with respect to scalability challenge that comes with HL-LHC on the horizon

The GridKa Tape System: status and outlook

Tape storage is still a cost effective way to keep large amounts of data over a long period of time and it is expected that this will continue in the future. The GridKa tape environment is a complex system of many hardware components and software layers. Configuring this system for optimal performance for all use cases is a non-trivial task and requires a lot of experience. We present the current status of the GridKa tape environment, report on recent upgrades and improvements and plans to further develop and enhance the system, especially with regard to the future requirements of the HEP experiments and their large data centers. The short-term planning mainly includes the transition from TSM to HPSS as the backend and the effects on the connection of dCache and xrootd. Recent changes of the vendor situation of certain tape technologies require a precise analysis of the impact and eventual adaptation of the mid-term planning, in particular with respect to scalability challenge that comes with HL-LHC on the horizon