Low oxygen stress dynamically regulates the translation of cellular mRNAs as a means of energy conservation in seedlings of Arabidopsis thaliana. Most of the highly hypoxia-induced mRNAs are recruited to polysomes and actively translated, whereas other cellular mRNAs become translationally inactive and are either targeted for stabilization or degradation. Here we identify the involvement of OLIGOURIDYLATE BINDING PROTEIN 1 (UBP1), a triple RNA Recognition Motif protein, in dynamic and reversible aggregation of translationally repressed mRNAs during hypoxia. Mutation or down-regulation of UBP1C interferes with seedling establishment and reduces survival of low oxygen stress. By use of messenger ribonucleoprotein (mRNP) immunopurification, we show that UBP1C constitutively binds a subpopulation of mRNAs characterized by uracil-rich 3′-untranslated regions under normoxic conditions. During hypoxia, UBP1C association with nonuracil-rich mRNAs is enhanced concomitant with its aggregation into microscopically visible cytoplasmic foci, referred to as UBP1 stress granules (SGs). This UBP1C-mRNA association occurs as global levels of protein synthesis decline. Upon reoxygenation, rapid UBP1 SG disaggregation coincides with the return of the stabilized mRNAs to polysomes. The mRNAs that are highly induced and translated during hypoxia largely circumvent UBP1C sequestration. Thus, UBP1 is established as a component of dynamically assembled cytoplasmic mRNPs that sequester mRNAs that are poorly translated during a transient low energy stress.ene expression in the model plant Arabidopsis thaliana is controlled at multiple levels from chromatin organization to protein modification. The selective translation of individual mRNAs can be a key regulatory step particularly in response to numerous environmental perturbations including hypoxia (1), hormones, and signaling pathway inhibitors (e.g., torin, an inhibitor of target of rapamycin kinase) (reviewed in ref. 2). In seedlings, hypoxia rapidly reduces the number of ribosomes engaged in translation, mirroring decreases in cellular ATP content (1). The mapping of ribosome footprints on mRNAs confirmed that this regulation largely occurs at initiation of translation (3). The comparison of steady-state and ribosome-associated mRNA levels obtained by translating ribosome affinity purification revealed that the majority of cellular mRNAs (ca. 90%) become poorly associated with ribosomes when seedlings are exposed to transient hypoxia. These translationally repressed mRNAs include 9% that are elevated at the steady-state level due to increased synthesis or stability, 21% that are reduced due to decreased synthesis or stability, and 65% with little or no change in abundance (1). Most of the repressed transcripts return to polysomes within 1 h of reoxygenation, demonstrating that they are safeguarded by some mechanism until reoxygenation. This study aimed to elucidate the molecular mechanism that underlies the dichotomy between well-and poorly translated mRNAs during hypoxia in Arabidop...

Background Malnutrition is a major contributor to disease burden in India. To inform subnational action, we aimed to assess the disease burden due to malnutrition and the trends in its indicators in every state of India in relation to Indian and global nutrition targets. Methods We analysed the disease burden attributable to child and maternal malnutrition, and the trends in the malnutrition indicators from 1990 to 2017 in every state of India using all accessible data from multiple sources, as part of Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. The states were categorised into three groups using their Socio-demographic Index (SDI) calculated by GBD on the basis of per capita income, mean education, and fertility rate in women younger than 25 years. We projected the prevalence of malnutrition indicators for the states of India up to 2030 on the basis of the 1990-2017 trends for comparison with India National Nutrition Mission (NNM) 2022 and WHO and UNICEF 2030 targets. Findings Malnutrition was the predominant risk factor for death in children younger than 5 years of age in every state of India in 2017, accounting for 68•2% (95% UI 65•8-70•7) of the total under-5 deaths, and the leading risk factor for health loss for all ages, responsible for 17•3% (16•3-18•2) of the total disability-adjusted life years (DALYs). The malnutrition DALY rate was much higher in the low SDI than in the middle SDI and high SDI state groups. This rate varied 6•8 times between the states in 2017, and was highest in the states of Uttar Pradesh, Bihar, Assam, and Rajasthan. The prevalence of low birthweight in India in 2017 was 21•4% (20•8-21•9), child stunting 39•3% (38•7-40•1), child wasting 15•7% (15•6-15•9), child underweight 32•7% (32•3-33•1), anaemia in children 59•7% (56•2-63•8), anaemia in women 15-49 years of age 54•4% (53•7-55•2), exclusive breastfeeding 53•3% (51•5-54•9), and child overweight 11•5% (8•5-14•9). If the trends estimated up to 2017 for the indicators in the NNM 2022 continue in India, there would be 8•9% excess prevalence for low birthweight, 9•6% for stunting, 4•8% for underweight, 11•7% for anaemia in children, and 13•8% for anaemia in women relative to the 2022 targets. For the additional indicators in the WHO and UNICEF 2030 targets, the trends up to 2017 would lead to 10•4% excess prevalence for wasting, 14•5% excess prevalence for overweight, and 10•7% less exclusive breastfeeding in 2030. The prevalence of malnutrition indicators, their rates of improvement, and the gaps between projected prevalence and targets vary substantially between the states. Interpretation Malnutrition continues to be the leading risk factor for disease burden in India. It is encouraging that India has set ambitious targets to reduce malnutrition through NNM. The trends up to 2017 indicate that substantially higher rates of improvement will be needed for all malnutrition indicators in most states to achieve the Indian 2022 and the global 2030 targets. The state-specific findings in this report indicate the...

The decay of mRNA plays a vital role in modulating mRNA abundance, which, in turn, influences cellular and organismal processes. In plants and metazoans, three distinct pathways carry out the decay of most cytoplasmic mRNAs: The mRNA decapping complex, which requires the scaffold protein VARICOSE (VCS), removes a protective 5' cap, allowing for 5' to 3' decay via EXORIBONUCLEASE4 (XRN4, XRN1 in metazoans and yeast), and both the exosome and SUPPRESSOR OF VCS (SOV)/DIS3L2 degrade RNAs in the 3' to 5' direction. However, the unique biological contributions of these three pathways, and whether they degrade specialized sets of transcripts, are unknown. In , the participation of SOV in RNA homeostasis is also unclear, because mutants have a normal phenotype. We carried out mRNA decay analyses in wild-type, ,, and seedlings, and used a mathematical modeling approach to determine decay rates and quantify gene-specific contributions of VCS and SOV to decay. This analysis revealed that VCS (decapping) contributes to decay of 68% of the transcriptome, and, while it initiates degradation of mRNAs with a wide range of decay rates, it especially contributes to decay of short-lived RNAs. Only a few RNAs were clear SOV substrates in that they decayed more slowly in mutants. However, 4,506 RNAs showed VCS-dependent feedback in that modulated decay rates, and, by inference, transcription, to maintain RNA abundances, suggesting that these RNAs might also be SOV substrates. This feedback was shown to be independent of siRNA activity.

Stresses from various environmental challenges continually confront plants, and their responses are important for growth and survival. One molecular response to such challenges involves the alternative polyadenylation of mRNA. In plants, it is unclear how stress affects the production and fate of alternative mRNA isoforms. Using a genome-scale approach, we show that in Arabidopsis thaliana, hypoxia leads to increases in the number of mRNA isoforms with polyadenylated 39 ends that map to 59-untranslated regions (UTRs), introns, and protein-coding regions. RNAs with 39 ends within protein-coding regions and introns were less stable than mRNAs that end at 39-UTR poly(A) sites. Additionally, these RNA isoforms were underrepresented in polysomes isolated from control and hypoxic plants. By contrast, mRNA isoforms with 39 ends that lie within annotated 59-UTRs were overrepresented in polysomes and were as stable as canonical mRNA isoforms. These results indicate that the generation of noncanonical mRNA isoforms is an important feature of the abiotic stress response. The finding that several noncanonical mRNA isoforms are relatively unstable suggests that the production of non-stop and intronic mRNA isoforms may represent a form of negative regulation in plants, providing a conceptual link with mechanisms that generate these isoforms (such as alternative polyadenylation) and RNA surveillance.