Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing

Most unwanted RNA transcripts in the nucleus of eukaryotic cells, such as splicing-defective pre-mRNAs and spliced-out introns, are rapidly degraded by the nuclear exosome. In budding yeast, a number of these unwanted RNA transcripts, including spliced-out introns, are first recognized by the nuclear exosome cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent nuclear-exosome-mediated degradation. However, it remains unclear when spliced-out introns are recognized by TRAMP, and whether TRAMP may have any potential roles in pre-mRNA splicing. Here, we demonstrated that TRAMP is cotranscriptionally recruited to nascent RNA transcripts, with particular enrichment at intronic sequences. Deletion of TRAMP components led to further accumulation of unspliced pre-mRNAs even in a yeast strain defective in nuclear exosome activity, suggesting a novel stimulatory role of TRAMP in splicing. We also uncovered new genetic and physical interactions between TRAMP and several splicing factors, and further showed that TRAMP is required for optimal recruitment of the splicing factor Msl5p. Our study provided the first evidence that TRAMP facilitates pre-mRNA splicing, and we interpreted this as a fail-safe mechanism to ensure the cotranscriptional recruitment of TRAMP before or during splicing to prepare for the subsequent targeting of spliced-out introns to rapid degradation by the nuclear exosome.link_to_OA_fulltex

Prognostic significance of Cytokeratin 20-positive lymph node vascular endothelial growth factor A mRNA and chromodomain helicase DNA binding protein 4 in pN0 colorectal cancer patients

2017-2018 > Academic research: refereed > Publication in refereed journal201808 bcrcVersion of RecordPublishe

Steady-state security in distribution networks with large wind farms

© 2014, The Author(s). Aging network assets, forced and unforced outages, and the way the networks are operated in a deregulated market are of significant concerns to integrate large wind farms in a distribution network. In many cases, the constrained network capacity is a potential barrier to the large-scale integration of wind power. This paper probabilistically assesses the steady-state security in a distribution network in the presence of large wind farms. The approach incorporates active distribution network operating conditions, including intermittent power outputs, random outages, demand fluctuations, and dynamic interactions and exchanges, and then assesses the steady state security using Monte Carlo simulation. A case study is performed by integrating large wind farms into a distribution network. The results suggest that intermittent outputs of large wind farms in a distribution network can impact the steady-state security considerably. However, the level of impact of wind farms does not necessarily correlate with the installed capacity of them

Carbon Capture and Renewables: Strategic Conflicts or Tactical Complementarities

While coal use is being challenged around the world, renewable energy is accelerating ahead and those who back the latter strongly often feel that any talk of finding ways to reduce the impact of continuing to use fossil fuel risks deflecting or slowing the growth of renewables. However, it is still the case that fossil fuels remain the dominant energy suppliers, and they will be so for some while. In which case, if carbon emission reduction is seen as urgent, then clean-up options are also urgent, if only perhaps as an interim measure. This chapter looks at some of the key options for abating emissions from the combustion of fossil fuel, focussing on the various types of carbon capture, their potentials and problems and possible conflicts or complementarities with renewables. While the prospects for carbon capture do not look good at present, it is argued that some of the technologies may have an interim role, but that is set in the context of diminishing reliance on fossil fuel

Emerging concepts in treating cartilage, osteochondral defects, and osteoarthritis of the knee and ankle

The management and treatment of cartilage lesions, osteochondral defects, and osteoarthritis remain a challenge in orthopedics. Moreover, these entities have different behaviors in different joints, such as the knee and the ankle, which have inherent differences in function, biology, and biomechanics. There has been a huge development on the conservative treatment (new technologies including orthobiologics) as well as on the surgical approach. Some surgical development upraises from technical improvements including advanced arthroscopic techniques but also from increased knowledge arriving from basic science research and tissue engineering and regenerative medicine approaches. This work addresses the state of the art concerning basic science comparing the knee and ankle as well as current options for treatment. Furthermore, the most promising research developments promising new options for the future are discussed.(undefined)info:eu-repo/semantics/publishedVersio