mRNAs containing the histone 3' stem-loop are degraded primarily by decapping mediated by oligouridylation of the 3' end

Metazoan replication-dependent histone mRNAs are only present in S-phase, due partly to changes in their stability. These mRNAs end in a unique stem–loop (SL) that is required for both translation and cell-cycle regulation. Previous studies showed that histone mRNA degradation occurs through both 5′→3′ and 3′→5′ processes, but the relative contributions are not known. The 3′ end of histone mRNA is oligouridylated during its degradation, although it is not known whether this is an essential step. We introduced firefly luciferase reporter mRNAs containing the histone 3′ UTR SL (Luc-SL) and either a normal or hDcp2-resistant cap into S-phase HeLa cells. Both mRNAs were translated, and translation initially protected the mRNAs from degradation, but there was a lag of ∼40 min with the uncleavable cap compared to ∼8 min for the normal cap before rapid decay. Knockdown of hDcp2 resulted in a similar longer lag for Luc-SL containing a normal cap, indicating that 5′→3′ decay is important in this system. Inhibition of DNA replication with hydroxyurea accelerated the degradation of Luc-SL. Knockdown of terminal uridyltransferase (TUTase) 4 but not TUTase 3 slowed the decay process, but TUTase 4 knockdown had no effect on destabilization of the mRNA by hydroxyurea. Both Luc-SL and its 5′ decay intermediates were oligouridylated. Preventing oligouridylation by 3′-deoxyadenosine (cordycepin) addition to the mRNA slowed degradation, in the presence or absence of hydroxyurea, suggesting oligouridylation initiates degradation. The spectrum of oligouridylated fragments suggests the 3′→5′ degradation machinery stalls during initial degradation, whereupon reuridylation occurs

Hsp70 chaperones: Cellular functions and molecular mechanism

Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100

The Lid Domain of Caenorhabditis elegans Hsc70 Influences ATP Turnover, Cofactor Binding and Protein Folding Activity

Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Increasing the efficiency of use of wheeled harrow units in regions of risk farming

Crop yields largely depend on the quality of the soil prepared for sowing. At the same time, one of the most important field operations is harrowing, with the main technological parameter of harrowing is the depth of processing of the fertile soil layer. Failure to do not have the necessary depth of processing leads to a decrease in yields, and the excess - to additional energy costs, and therefore to increase the cost of a unit of the resulting products. As you know, the main parameter influencing the depth of processing is the weight that falls on the working organ of the harrow. This article proposes a device that has obtained a patent for the intellectual property of the Russian Federation, allowing to regulate the weight of the working organ of the harrow, due to its optimal redistribution within the machine-tractor unit (MTU), and the theoretical and experimental results of the experimental harrowing unit are provided. The results suggest that the proposed solution is highly effective, which provides as an opportunity for quality pre-planting treatment, and contributes to the compliance with the necessary agro-technological requirements for the harrowing process

Animation and video in scientific publication

Abstract: The typical examples of multimedia in scientific publication are considered.Note: Research direction:Programming, parallel computing, multimedi