OsHYPK-mediated protein N-terminal acetylation coordinates plant development and abiotic stress responses in rice

N-terminal acetylation is one of the most common protein modifications in eukaryotes,and approximately 40%of human and plant proteomes are acetylated by ribosome-associated N-terminal acetyltransferase A(NatA)in a co-translational manner.However,the in vivo regulatory mechanism of NatA and the global impact of NatA-mediated N-terminal acetylation on protein fate remain unclear.Here,we identify Huntingtin Yeast partner K(HYPK),an evolutionarily conserved chaperone-like protein,as a positive regulator of NatA activity in rice.We found that loss of OsHYPK function leads to developmental defects in rice plant architecture but increased resistance to abiotic stresses,attributable to perturbation of the N-terminal acetylome and accelerated global protein turnover.Furthermore,we demonstrated that OsHYPK is also a substrate of NatA and that N-terminal acetylation of OsHYPK promotes its own degradation,probably through the Ac/N-degron pathway,which could be induced by abiotic stresses.Taken together,our findings suggest that the OsHYPK-NatA complex plays a critical role in coordinating plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover,which are essential for maintaining adaptive phenotypic plasticity in rice.

Regulation of RNase E during the UV stress response in the cyanobacterium Synechocystis sp.PCC 6803

Endoribonucleases govern the maturation and degradation of RNA and are indispensable in the posttranscriptional regulation of gene expression.A key endoribonuclease in Gram-negative bacteria is RNase E.To ensure an appropriate supply of RNase E,some bacteria,such as Escherichia coli,feedback-regulate RNase E expression via the rne 5′-untranslated region(5′UTR)in cis.However,the mechanisms involved in the control of RNase E in other bacteria largely remain unknown.Cyanobacteria rely on solar light as an energy source for photosynthesis,despite the inherent ultraviolet(UV)irradiation.In this study,we first investigated globally the changes in gene expression in the cyanobacterium Synechocystis sp.PCC ^(6)803 after a brief exposure to UV.Among the 407 responding genes 2 h after UV exposure was a prominent upregulation of rne mRNA level.Moreover,the enzymatic activity of RNase E rapidly increased as well,although the protein stability decreased.This unique response was underpinned by the increased accumulation of full-length rne mRNA caused by the stabilization of its 5′UTR and suppression of premature transcriptional termination,but not by an increased transcription rate.Mapping of RNA 3′ends and in vitro cleavage assays revealed that RNase E cleaves within a stretch of six consecutive uridine residues within the rne 5′UTR,indicating autoregulation.These observations suggest that RNase E in cyanobacteria contributes to reshaping the transcriptome during the UV stress response and that its required activity level is secured at the RNA level despite the enhanced turnover of the protein.

Paradigms and Paradox in the Ethylene Signaling Pathway and Interaction Network

Phytohormone ethylene plays pivotal roles in plant response to developmental and environmental signals. During the past few years, the emerging evidence has led us to a new understanding of the signaling mechanisms and regulatory networks of the ethylene action. In this review, we focus on the major advances made in the past three years, particularly the findings leading to new paradigms and the observations under debate. With the recent demonstration of the regulation of the protein stability of numerous key signaling components including EIN3, ELL1, EIN2, ETR2, EBFI/EBF2, and ETPI/ETP2, we highlight proteasome-dependent protein degradation as an essential regulatory mechanism that is widely adopted in the ethylene signaling pathway. We also discuss the implication of the negative feedback mechanism in the ethylene signaling pathway in light of ethylene-induced ETR2 and EBF2 gene expression. Meanwhile, we summarize the controversy on the involvement of MKK9-MPK3/6 cascade in the ethylene signaling versus biosynthesis pathway, and discuss the possible role of this MAPK module in the ethylene action. Finally, we describe the complex interactions between ethylene and other signaling pathways including auxin, light, and plant innate immunity, and propose that EIN3/ EIL1 act as a convergence point in the ethylene-initiated signaling network.

Exercise as a therapy for cancer-induced muscle wasting

Cancer cachexia is a progressive disorder characterized by body weight,fat,and muscle loss.Cachexia induces metabolic disruptions that can be analogous and distinct from those observed in cancer,obscuring both diagnosis and treatment options.Inflammation,hypogonadism,and physical inactivity are widely investigated as systemic mediators of cancer-induced muscle wasting.At the cellular level,dysregulation of protein turnover and energy metabolism can negatively impact muscle mass and function.Exercise is well known for its anti-inflammatory effects and potent stimulation of anabolic signaling.Emerging evidence suggests the potential for exercise to rescue muscle's sensitivity to anabolic stimuli,reduce wasting through protein synthesis modulation,myokine release,and subsequent downregulation of proteolytic factors.To date,there is no recommendation for exercise in the management of cachexia.Given its complex nature,a multimodal approach incorporating exercise offers promising potential for cancer cachexia treatment.This review's primary objective is to summarize the growing body of research examining exercise regulation of cancer cachexia.Furthermore,we will provide evidence for exercise interactions with established systemic and cellular regulators of cancer-induced muscle wasting.

Effects of PGC-1αoverexpression on the myogenic response during skeletal muscle regeneration

The ability of skeletal muscle to regenerate from injury is crucial for locomotion,metabolic health,and quality of life.Peroxisome proliferator-activated receptor-γcoactivator-1α(PGC1A)is a transcriptional coactivator required for mitochondrial biogenesis.Increased mitochondrial biogenesis is associated with improved muscle cell differentiation,however PGC1A's role in skeletal muscle regeneration following damage requires further investigation.The purpose of this study was to investigate the role of skeletal muscle-specific PGC1A overexpression during regeneration following damage.22 C57BL/6J(WT)and 26 PGC1A muscle transgenic(A1)mice were injected with either phosphate-buffered saline(PBS,uninjured control)or Bupivacaine(MAR,injured)into their tibialis anterior(TA)muscle to induce skeletal muscle damage.TA muscles were extracted 3-or 28-days postinjury and analyzed for markers of regenerative myogenesis and protein turnover.Pgc1a mRNA was~10–20 fold greater in A1 mice.Markers of protein synthesis,AKT and 4EBP1,displayed decreases in A1 mice compared to WT at both timepoints indicating a decreased protein synthetic response.Myod mRNA was~75%lower compared to WT 3 days post-injection.WT mice exhibited decreased cross-sectional area of the TA muscle at 28 days post-injection with bupivacaine compared to all other groups.PGC1A overexpression modifies the myogenic response during regeneration.

Development and progression of cancer cachexia:Perspectives from bench to bedside

Cancer cachexia(CC)is a devastating syndrome characterized by weight loss,reduced fat mass and muscle mass that affects approximately 80%of cancer patients and is responsible for 22%-30%of cancer-associated deaths.Understanding underlying mechanisms for the development of CC are crucial to advance therapies to treat CC and improve cancer outcomes.CC is a multi-organ syndrome that results in extensive skeletal muscle and adipose tissue wasting;however,CC can impair other organs such as the liver,heart,brain,and bone as well.A considerable amount of CC research focuses on changes that occur within the muscle,but cancer-related impairments in other organ systems are understudied.Furthermore,metabolic changes in organ systems other than muscle may contribute to CC.Therefore,the purpose of this review is to address degenerative mechanisms which occur during CC from a whole-body perspective.Outlining the information known about metabolic changes that occur in response to cancer is necessary to develop and enhance therapies to treat CC.As much of the current evidences in CC are from pre-clinical models we should note the majority of the data reviewed here are from preclinical models.