Most transcripts in growing cells are ribosomal RNA precursors (pre-rRNA). Here, we show that in mammals, aberrant pre-rRNA transcripts generated by RNA polymerase I (Pol I) are polyadenylated and accumulate markedly after treatment with low concentrations of actinomycin D (ActD), which blocks the synthesis of full-length rRNA. The poly(A) polymerase-associated domain-containing protein 5 is required for polyadenylation, whereas the exosome is partly responsible for the degradation of the short aberrant transcripts. Thus, polyadenylation functions in the quality control of Pol I transcription in metazoan cells. The impact of excessive aberrant RNAs on the degradation machinery is an unrecognized mechanism that might contribute to biological properties of ActD.
Climate actions can advance sustainable development
The COVID-19 pandemic and Russia’s war on Ukraine have impacted the global economy, including the energy sector. The pandemic caused drastic fluctuations in energy demand, oil price shocks, disruptions in energy supply chains, and hampered energy investments, while the war left the world with energy price hikes and energy security challenges. The long-term impacts of these crises on low-carbon energy transitions and mitigation of climate change are still uncertain but are slowly emerging. This paper analyzes the impacts throughout the energy system, including upstream fuel supply, renewable energy investments, demand for energy services, and implications for energy equity, by reviewing recent studies and consulting experts in the field. We find that both crises initially appeared as opportunities for low-carbon energy transitions: the pandemic by showing the extent of lifestyle and behavioral change in a short period and the role of science-based policy advice, and the war by highlighting the need for greater energy diversification and reliance on local, renewable energy sources. However, the early evidence suggests that policymaking worldwide is focused on short-term, seemingly quicker solutions, such as supporting the incumbent energy industry in the post-pandemic era to save the economy and looking for new fossil fuel supply routes for enhancing energy security following the war. As such, the fossil fuel industry may emerge even stronger after these energy crises creating new lock-ins. This implies that the public sentiment against dependency on fossil fuels may end as a lost opportunity to translate into actions toward climate-friendly energy transitions, without ambitious plans for phasing out such fuels altogether. We propose policy recommendations to overcome these challenges toward achieving resilient and sustainable energy systems, mostly driven by energy services
Biogenesis of eukaryotic ribosomes requires a number of RNA helicases that drive molecular rearrangements at various points of the assembly pathway. While many ribosome synthesis factors are conserved among all eukaryotes, certain features of ribosome maturation, such as U8 snoRNA-assisted processing of the 5.8S and 28S rRNA precursors, are observed only in metazoan cells. Here, we identify the mammalian DEAD box helicase family member Ddx51 as a novel ribosome synthesis factor and an interacting partner of the nucleolar GTP-binding protein Nog1. Unlike any previously studied yeast helicases, Ddx51 is required for the formation of the 3 end of 28S rRNA. Ddx51 binds to pre-60S subunit complexes and promotes displacement of U8 snoRNA from pre-rRNA, which is necessary for the removal of the 3 external transcribed spacer from 28S rRNA and productive downstream processing. These data demonstrate the emergence of a novel factor that facilitates a pre-rRNA processing event specific for higher eukaryotes.Synthesis of ribosomes is a highly complicated process that consumes a large amount of cellular resources and requires a large array of auxiliary factors. rRNAs, the main structural component of the ribosome, are transcribed as precursors (pre-rRNAs) that are processed to mature forms through cleavages, exonucleolytic trimming, and nucleotide modifications (34). Studies in the yeast Saccharomyces cerevisiae have led to the identification of more than 150 proteins acting in pre-rRNA processing and ribosome assembly (reviewed in references 14, 22, and 33). A variety of putative helicases, GTPases, and ATPases identified among ribosome synthesis factors are believed to facilitate extensive rearrangements in RNA and RNA-protein complexes occurring in the course of ribosome maturation (52). Functions of the majority of ribosome synthesis factors are still not completely understood. Based on sequence similarity, many yeast ribosome assembly factors have putative orthologs in higher eukaryotic species including humans (23). The overall pathway for ribosome maturation has also been conserved in eukaryotic evolution, but there are differences between organisms in the organization of the nucleolus (55) and pre-rRNA processing steps (12), pointing to the underlying mechanistic variations in this process.In addition to protein factors, several dozen to hundreds of small nucleolar RNAs (snoRNAs) participate in eukaryotic ribosome maturation (reviewed in references 3, 16, and 31).The majority of snoRNAs act as guides for posttranscriptional nucleotide modifications in rRNA (2Ј-O-ribose methylation or pseudouridylation) that fine-tune ribosome performance (13, 30, 39). However, several snoRNAs, including U3, U14, and U17/snR30, are required for cleavages within pre-rRNA and therefore are essential for ribosome production and cell viability (2,24,28,37,42). Two additional snoRNAs, U8 and U22, participate in rRNA cleavages in vertebrates (44, 59), underscoring variability in the pre-rRNA processing machinery between different eukaryotes...
Helminth parasites bias host CD4(+) T helper (Th) cells toward Th2 responses, drive alternative activation of macrophages, and expand T regulatory cells. Helminth-expressed carbohydrates play critical roles in driving much of this immune cell biasing. Studies on helminth glycans have focused on Lewis X, LDN, LDN-DF, other fucosylated structures, chitin, tyvelose, and trehalose, which interact with host antigen presenting cells (APCs) minimally via C-type lectins and/or Toll-like receptors (TLR). Here, we review recent findings on helminth glycan activation of APCs via C-type lectin/TLRs and introduce the concept that glycosylated helminth molecules require endocytosis to function as immune modulators. Second, we describe unpublished data showing that in vivo glycoconjugates comprising multiple copies of glycans on carriers are directly immune modulatory. Lastly, we discuss the observation that CD14 negatively regulates alternative activation of APCs during helminth infection. We close with a discussion on the use of immune modulatory glycans as vaccine adjuvants and as antiinflammatory therapeutics.
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