Deletion of translin (Tsn) induces robust adiposity and hepatic steatosis without impairing glucose tolerance.

OBJECTIVE: Translin knockout (KO) mice display robust adiposity. Recent studies indicate that translin and its partner protein, trax, regulate the microRNA and ATM kinase signaling pathways, both of which have been implicated in regulating metabolism. In the course of characterizing the metabolic profile of these mice, we found that they display normal glucose tolerance despite their elevated adiposity. Accordingly, we investigated why translin KO mice display this paradoxical phenotype. METHODS: To help distinguish between the metabolic effects of increased adiposity and those of translin deletion per se, we compared three groups: (1) wild-type (WT), (2) translin KO mice on a standard chow diet, and (3) adiposity-matched WT mice that were placed on a high-fat diet until they matched translin KO adiposity levels. All groups were scanned to determine their body composition and tested to evaluate their glucose and insulin tolerance. Plasma, hepatic, and adipose tissue samples were collected and used for histological and molecular analyses. RESULTS: Translin KO mice show normal glucose tolerance whereas adiposity-matched WT mice, placed on a high-fat diet, do not. In addition, translin KO mice display prominent hepatic steatosis that is more severe than that of adiposity-matched WT mice. Unlike adiposity-matched WT mice, translin KO mice display three key features that have been shown to reduce susceptibility to insulin resistance: increased accumulation of subcutaneous fat, increased levels of circulating adiponectin, and decreased Tnfα expression in hepatic and adipose tissue. CONCLUSIONS: The ability of translin KO mice to retain normal glucose tolerance in the face of marked adipose tissue expansion may be due to the three protective factors noted above. Further studies aimed at defining the molecular bases for this combination of protective phenotypes may yield new approaches to limit the adverse metabolic consequences of obesity.

Deletion of the microRNA-degrading nuclease, translin/trax, prevents pathogenic vascular stiffness.

Vascular stiffness plays a key role in the pathogenesis of hypertension. Recent studies indicate that the age-associated reduction in miR-181b levels in vascular smooth muscle cells (VSMCs) contributes to increased vascular stiffness. As these findings suggest that inhibiting degradation of miR-181b might prevent vascular stiffening, we have assessed whether the microRNA-degrading translin/trax (TN/TX) complex mediates degradation of miR-181b in the aorta.We found that TN-/- mice display elevated levels of miR-181b expression in the aorta. Therefore, we tested whether TN deletion prevents vascular stiffening in a mouse model of hypertension, induced by chronic high-salt intake (4%NaCl in drinking water for 3 wk; HSW). TN-/- mice subjected to HSW stress do not show increased vascular stiffness, as monitored by pulse wave velocity and tensile testing. The protective effect of TN deletion in the HSW paradigm appears to be mediated by its ability to increase miR-181b in the aorta since HSW decreases levels of miR-181b in WT mice, but not in TN KO mice. We demonstrate for the first time that interfering with microRNA degradation can have a beneficial impact on the vascular system and identify the microRNA-degrading TN/TX RNase complex as a potential therapeutic target in combatting vascular stiffness.NEW & NOTEWORTHY While the biogenesis and mechanism of action of mature microRNA are well understood, much less is known about the regulation of microRNA via degradation. Recent studies have identified the protein complex, translin(TN)/trax(TX), as a microRNA-degrading enzyme. Here, we demonstrate that TN/TX is expressed in vascular smooth muscle cells. Additionally, deletion of the TN/TX complex selectively increases aortic miR-181b and prevents increased vascular stiffness caused by ingestion of high-salt water. To our knowledge, this is first report describing the role of a microRNA RNAse in cardiovascular biology or pathobiology.

Trax: A versatile signaling protein plays key roles in synaptic plasticity and DNA repair.

Translin-associated protein X (TSNAX), also called trax, was first identified as a protein that interacts with translin. Subsequent studies demonstrated that these proteins form a heteromeric RNase complex that mediates degradation of microRNAs, a pivotal finding that has stimulated interest in understanding the role of translin and trax in cell signaling. Recent studies addressing this question have revealed that trax plays key roles in both synaptic plasticity and DNA repair signaling pathways. In the context of synaptic plasticity, trax works together with its partner protein, translin, to degrade a subset of microRNAs. Activation of the translin/trax RNase complex reverses microRNA-mediated translational silencing to trigger dendritic protein synthesis critical for synaptic plasticity. In the context of DNA repair, trax binds to and activates ATM, a central component of the double-stranded DNA repair process. Thus, these studies focus attention on trax as a critical signaling protein that interacts with multiple partners to impact diverse signaling pathways. To stimulate interest in deciphering the multifaceted role of trax in cell signaling, we summarize the current understanding of trax biology and highlight gaps in our knowledge about this protean protein.

Rapid reversal of translational silencing: Emerging role of microRNA degradation pathways in neuronal plasticity.

As microRNAs silence translation, rapid reversal of this process has emerged as an attractive mechanism for driving de novo protein synthesis mediating neuronal plasticity. Herein, we summarize recent studies identifying neuronal stimuli that trigger rapid decreases in microRNA levels and reverse translational silencing of plasticity transcripts. Although these findings indicate that neuronal stimulation elicits rapid degradation of selected microRNAs, we are only beginning to decipher the molecular pathways involved. Accordingly, we present an overview of several molecular pathways implicated in mediating microRNA degradation: Lin-28, translin/trax, and MCPIP1. As these degradation pathways target distinct subsets of microRNAs, they enable neurons to reverse silencing rapidly, yet selectively.

Fever with thrombocytopenia associated with a novel bunyavirus in China.

BACKGROUND: Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing. METHODS: We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples. RESULTS: We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness. CONCLUSIONS: A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).

Adenosine A2A Receptor Regulates microRNA-181b Expression in Aorta: Therapeutic Implications for Large-Artery Stiffness.

Background The identification of large-artery stiffness as a major, independent risk factor for cardiovascular disease-associated morbidity and death has focused attention on identifying therapeutic strategies to combat this disorder. Genetic manipulations that delete or inactivate the translin/trax microRNA-degrading enzyme confer protection against aortic stiffness induced by chronic ingestion of high-salt water (4%NaCl in drinking water for 3 weeks) or associated with aging. Therefore, there is heightened interest in identifying interventions capable of inhibiting translin/trax RNase activity, as these may have therapeutic efficacy in large-artery stiffness. Methods and Results Activation of neuronal adenosine A2A receptors (A2ARs) triggers dissociation of trax from its C-terminus. As A2ARs are expressed by vascular smooth muscle cells (VSMCs), we investigated whether stimulation of A2AR on vascular smooth muscle cells promotes the association of translin with trax and, thereby increases translin/trax complex activity. We found that treatment of A7r5 cells with the A2AR agonist CGS21680 leads to increased association of trax with translin. Furthermore, this treatment decreases levels of pre-microRNA-181b, a target of translin/trax, and those of its downstream product, mature microRNA-181b. To check whether A2AR activation might contribute to high-salt water-induced aortic stiffening, we assessed the impact of daily treatment with the selective A2AR antagonist SCH58261 in this paradigm. We found that this treatment blocked aortic stiffening induced by high-salt water. Further, we confirmed that the age-associated decline in aortic pre-microRNA-181b/microRNA-181b levels observed in mice also occurs in humans. Conclusions These findings suggest that further studies are warranted to evaluate whether blockade of A2ARs may have therapeutic potential in treating large-artery stiffness.

An outbreak of Mycoplasma pneumoniae caused by a macrolide-resistant isolate in a nursery school in China.

Eighteen out of 45 children were reported to have a respiratory illness during an outbreak at a temporary dormitory in a nursery school in China in 2011. To study the outbreak and to determine the risk factors for infection, an epidemiological investigation was performed. A standardized questionnaire was completed for a total of 45 children with the help of their guardians and parents. In addition, acute- and convalescent-phase serum samples and throat swabs from the children were taken for laboratory diagnosis. The diagnosis of a Mycoplasma-like illness was based on the following clinical criteria. The criteria were onset of illness after 31 May 2011, characterized by a cough, fever(>37.5 °C), or at least 3 of the following symptoms: fever, sore throat, cough or expectoration, and runny or stuffy nose. PCR-restriction fragment length polymorphism (PCR-RFLP), determination of MICs, and sequencing were performed to determine the genotype, antibiotic resistance, and sequence polymorphisms of the isolated strains, respectively. The paired sera revealed that 15 patients were infected with Mycoplasma pneumoniae. Epidemiology confirmed that this was a point source outbreak, characterized by a short incubation period, a high secondary attack rate, and a long period of hospitalization. PCR-RFLP analysis revealed that the 12 isolated strains of M. pneumoniae shared the same subtype P1 gene, and 23S rRNA sequence analysis showed that these strains harbored two macrolide-resistant gene-related point mutations at position 2063 and 2617. In this outbreak, the major risk factor was the distance between the bed of the first patient and the beds of close contacts (beds less than three meters apart). The strains isolated in this study were found to harbor two point mutations conferring macrolide resistance, indicating the importance of pathogen and drug resistance surveillance systems.

High Carriage of Extended-Spectrum, Beta Lactamase-Producing, and Colistin-Resistant Enterobacteriaceae in Tibetan Outpatients with Diarrhea.

Antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) have been detected in human-impacted habitats, especially in densely populated cities. The Qinghai-Tibet Plateau is located far from the heavily populated regions of China, and Tibetan residents have distinct dietary habits and gut microbes. Antibiotic-resistance monitoring in the Tibetan population is rare. Here, we collected stool samples from Tibetan outpatients with diarrhea. From 59 samples, 48 antibiotic-resistant Enterobacteriaceae isolates were obtained, including 19 extended-spectrum beta lactamase (ESBL)-producing isolates from 16 patients and 29 polymyxin-resistant isolates from 22 patients. Either ESBL or mcr genes were found in 17 Escherichia coli isolates, approximately 58.8% of which were multidrug-resistant, and ten incompatible plasmid types were found. The gene blaCTX-M was a common genotype in the ESBL-producing E. coli isolates. Four E. coli isolates contained mcr-1. The same mcr-1-carrying plasmid was found in distinct E. coli isolates obtained from the same sample, thus confirming horizontal transmission of mcr-1 between bacteria. Genomic clustering of E. coli isolates obtained from Lhasa, with strains from other regions providing evidence of clone spreading. Our results reveal a strong presence of ARB and ARGs in Tibetan outpatients with diarrhea, implying that ARB and ARGs should be monitored in the Tibetan population.

Elevated body fat increases amphetamine accumulation in brain: evidence from genetic and diet-induced forms of adiposity.

Despite the high prevalence of obesity, little is known about its potential impact on the pharmacokinetics of psychotropic drugs. In the course of investigating the role of the microRNA system on neuronal signaling, we found that mice lacking the translin/trax microRNA-degrading enzyme display an exaggerated locomotor response to amphetamine. As these mice display robust adiposity in the context of normal body weight, we checked whether this phenotype might reflect elevated brain levels of amphetamine. To assess this hypothesis, we compared plasma and brain amphetamine levels of wild type and Tsn KO mice. Furthermore, we checked the effect of diet-induced increases in adiposity on plasma and brain amphetamine levels in wild type mice. Brain amphetamine levels were higher in Tsn KO mice than in wild type littermates and correlated with adiposity. Analysis of the effect of diet-induced increases in adiposity in wild type mice on brain amphetamine levels also demonstrated that brain amphetamine levels correlate with adiposity. Increased adiposity displayed by Tsn KO mice or by wild type mice fed a high-fat diet correlates with elevated brain amphetamine levels. As amphetamine and its analogues are widely used to treat attention deficit disorder, which is associated with obesity, further studies are warranted to assess the impact of adiposity on amphetamine levels in these patients.

Degradation of Premature-miR-181b by the Translin/Trax RNase Increases Vascular Smooth Muscle Cell Stiffness.

[Figure: see text].

Multilocus outbreak of foodborne botulism linked to contaminated sausage in Hebei province, China.

In 2007, an outbreak of foodborne botulism occurred in Hebei province, China. An epidemiological investigation and laboratory detection studies showed that sausage contaminated by type A Clostridium botulinum caused this outbreak of food poisoning. Its clinical and epidemiological features were different from previous reports of food poisoning.

Scrub typhus in previously unrecognized areas of endemicity in China.

Scrub typhus, caused by Orientia tsutsugamushi, has emerged recently in areas of northern China where the disease had not been known to exist. We analyzed epidemiological, clinical, and laboratory data for 104 patients who were admitted to a hospital in Fuyang City between 26 September and 1 November 2008. We showed that the major clinical manifestations of the patients were fever (100%), headache (82%), myalgias (77%), eschar (67%), rash (52%), and unusual facial flushing (62%). Among the 104 patients, the sera of 98% contained IgM antibodies to O. tsutsugamushi detected by indirect immunofluorescence assays (IFA), and DNA of the O. tsutsugamushi 56-kDa gene was amplified by PCR from the blood of 36 patients. We conclude that 104 patients were infected with scrub typhus in Fuyang City, Anhui Province. Our study indicates that physicians need to consider the diagnosis of scrub typhus for febrile patients living in northern China, where scrub typhus had not been considered to exist in the past.

Genetic inactivation of the translin/trax microRNA-degrading enzyme phenocopies the robust adiposity induced by Translin (Tsn) deletion.

OBJECTIVE: Deletion of Translin (Tsn) from mice induces an unusual metabolic profile characterized by robust adiposity, normal body weight and glucose tolerance. Translin (TN) protein and its partner, trax (TX), form the TN/TX microRNA-degrading enzyme. Since the microRNA system plays a prominent role in regulating metabolism, we reasoned that the metabolic profile displayed by Tsn KO mice might reflect dysregulation of microRNA signaling. METHODS: To test this hypothesis, we inserted a mutation, E126A, in Tsnax, the gene encoding TX, that abolishes the microRNA-degrading enzymatic activity of the TN/TX complex. In addition, to help define the cell types that drive the adiposity phenotype, we have also generated mice with floxed alleles of Tsn or Tsnax. RESULTS: Introduction of the E126A mutation in Tsnax does not impair expression of TN or TX proteins or their co-precipitation. Furthermore, these mice display selective increases in microRNAs that match those induced by Tsn deletion, confirming that this mutation in Tsnax inactivates the microRNA-degrading activity of the TN/TX complex. Mice homozygous for the Tsnax (E126A) mutation display a metabolic profile that closely mimics that of Tsn KO mice. Selective deletion of Tsn or Tsnax from either adipocytes or hepatocytes, two candidate cell types, does not phenocopy the elevated adiposity displayed by mice with constitutive Tsn deletion or the Tsnax (E126A) mutation. Furthermore, global, conditional deletion of Tsn in adulthood does not elicit increased adiposity. CONCLUSION: Taken together, these findings indicate that inactivation of the TN/TX microRNA-degrading enzyme during development is necessary to drive the robust adiposity displayed by Tsn KO mice.

Rickettsial Seroepidemiology among farm workers, Tianjin, People's Republic of China.

High seroprevalence rates for Anaplasma phagocytophilum (8.8%), Coxiella burnetii (6.4%), Bartonella henselae (9.6%), and Rickettsia typhi (4.1%) in 365 farm workers near Tianjin, People's Republic of China, suggest that human infections with these zoonotic bacteria are frequent and largely unrecognized. Demographic features of seropositive persons suggest distinct epidemiology, ecology, and risks.

Nosocomial transmission of human granulocytic anaplasmosis in China.

CONTEXT: Human granulocytic anaplasmosis (HGA) is an emerging tick-borne disease in China. A cluster of cases among health care workers and family members following exposure to a patient with fulminant disease consistent with HGA prompted investigation. OBJECTIVE: To investigate the origin and transmission of apparent nosocomial cases of febrile illness in the Anhui Province. DESIGN, SETTING, AND PATIENTS: After exposure to an index patient whose fatal illness was characterized by fever and hemorrhage at a primary care hospital and regional tertiary care hospital's isolation ward, secondary cases with febrile illness who were suspected of being exposed were tested for antibodies against Anaplasma phagocytophilum and by polymerase chain reaction (PCR) and DNA sequencing for A. phagocytophilum DNA. Potential sources of exposure were investigated. MAIN OUTCOME MEASURE: Cases with serological or PCR evidence of HGA were compared with uninfected contacts to define the attack rate, relative risk of illness, and potential risks for exposure during the provision of care to the index patient. RESULTS: In a regional hospital of Anhui Province, China, between November 9 and 17, 2006, a cluster of 9 febrile patients with leukopenia, thrombocytopenia, and elevated serum aminotransferase levels were diagnosed with HGA by PCR for A. phagocytophilum DNA in peripheral blood and by seroconversion to A. phagocytophilum. No patients had tick bites. All 9 patients had contact with the index patient within 12 hours of her death from suspected fatal HGA while she experienced extensive hemorrhage and underwent endotracheal intubation. The attack rate was 32.1% vs 0% (P = .04) among contacts exposed at 50 cm or closer, 45% vs 0% (P = .001) among those exposed for more than 2 hours, 75% vs 0% (P < .001) among those reporting contact with blood secretions, and 87.5% vs 0% (P = .004) among those reporting contact with respiratory secretions from the index patient. CONCLUSION: We report the identification of HGA in China and likely nosocomial transmission of HGA from direct contact with blood or respiratory secretions.

Multiple Pathways Mediate MicroRNA Degradation: Focus on the Translin/Trax RNase Complex.

The discovery of the microRNA system has revolutionized our understanding of translational control. Furthermore, growing appreciation of the pivotal role that de novo translation plays in activity-dependent synaptic plasticity has fueled interest among neuroscientists in deciphering how the microRNA system impacts neuronal signaling and the pathophysiology of neuropsychiatric disorders. Although we have a general understanding of how the microRNA system operates, many key questions remain. In particular, the biosynthesis of microRNAs and their role in translational silencing are fairly well understood. However, much less is known about how microRNAs are degraded and silencing is reversed, crucial aspects of microRNA signaling. In contrast to microRNA synthesis which is mediated almost exclusively by a single pathway that culminates in Dicer, recent studies indicate that there are multiple pathways of microRNA degradation that target different subpopulations of microRNAs. While the Lin-28 pathway of microRNA degradation has been investigated extensively, the translin/trax RNase complex has emerged recently as another pathway mediating microRNA degradation. Accordingly, we summarize herein key features of the translin/trax RNase complex as well as important gaps in our understanding of its regulation and function that are the focus of ongoing studies.

Molecular epidemic survey on co-prevalence of scrub typhus and marine typhus in Yuxi city, Yunnan province of China.

BACKGROUND: Human rickettsioses are worldwide zoonoses and it is not easy to differentiate them from other infectious diseases because of their atypical manifestation. In recent years the number of patients with fever of unknown causes from Hongta District CDC, Yuxi city of Yunnan Province has been increasing significantly in the summer. Diagnosis of scrub typhus was made by local clinicians. In order to ascertain the disease, we undertook a laboratory investigation for such patients from August 18 to 26, 2005. METHODS: Active surveillance was conducted by Hongta District CDC Yuxi city of Yunnan Province from 2002 to 2004 and basic data were obtained from cases confirmed according to clinical definitions. Average incidences and town-level incidences were calculated during the study periods. Blood samples were analyzed by PCR and serological test. Based on the groEL gene sequences a paired general outer primers (Gro-1 and Gro-2) targeting typhus, spotted fever as well as scrub typhus and two paired inner primers (SF1, SR2 and TF1, TR2) for typhus together with spotted fever and scrub typhus, respectively, were designed to perform a multiplex-nested PCR. Serological assay was carried out by indirect immunofluorescence assay with 7 different rickettsial antigens, i.e., R.mossori, R.sibirica, R.conorii, O.tsutsugamushi, B.quintana, B.henselae and Coxilella burnetii phase II Ag. RESULTS: Epidemiological surveillance showed that from 2002 to 2004, the average incidences of the scrub typhus or scrub typhus with murine typhus were 222.1/10(5), 204.3/10(5) and 109.6/10(5), respectively. Of 13 blood samples taken during acute stage of illness, 6 showed the amplified products for scrub typhus and the sequenced products showed 100%, 99%, 99%, 99%, 99%, 99% similarity to O.tsutsugamushi Karp but they shared the same deduced amino acid sequences, which indicated 100% identity with the heat shock protein of the O.tsutsugamushi Karp strain. Five yielded PCR products for murine typhus and their corresponding nucleotide sequences exhibited 100%, 100%, 99%, 99% and 99% similarity to R. mossori Wilmington and the analyses of predicted amino acid sequences indicated 100%, 100%, 98%, 98% and 98% identity with the heat shock protein of R. mossori Wilmington strain. Of the 8 PCR positive patients, 3 showed a co-infection of scrub typhus with murine typhus. All the 13 serum samples from febrile patients were positive against O. tsutsugamushi and 8 of them were positive against R. mossori. All of the 8 paired specimens had four-fold elevation of antibody against O. tsutsugamushi, and seroconversion for typhus was demonstrated in 3 paired serum samples. Another finding in the study was that a high seropositive prevalence (76.9%) of Q fever was detected. CONCLUSION: It's confirmed that co-prevalence of scrub typhus with murine typhus are occurring in Yuxi city of Yunnan province, China. Other rickettsial diseases also need to be investigated in these areas.

Follow-up analysis on the epidemic strains of Orientia tsutsugamushi in the first outbreak of scrub typhus in Henan Province, China.

To obtain knowledge of the genetic characteristics and types of the epidemic strains of Orientia tsutsugamushi in the first outbreak of scrub typhus in Henan Province, genus and type-specific primers were employed to amplify a fragment of the gene of 56 kDa protein. Serotyping demonstrated that, of the 19 patients [15 patients in recovery phase (10-40 days) and 4 of patients in acute phase (1-7 days)], 4 were infected with Gilliam type, 8 with Kato type, 6 with Karp type, and 1 with an unknown type. Successful genotyping was obtained for only 3 patients, indicating that 2 were infected with Karp type and 1 with Taiwan Kato type. Thus the outbreak of scrub typhus in Henan Province was caused by at least two epidemic strains.

The Outer Membrane Protein OmpW Enhanced V. cholerae Growth in Hypersaline Conditions by Transporting Carnitine.

Pathogenic marine bacteria are found in environments and food sources with high salt concentrations, which the bacteria must effectively manage for their survival. Several mechanisms, such as the transport of ions and compatible solutes as well as changes in aerobic and anaerobic respiration, confer salt tolerance to bacteria. In this study, we found that the outer membrane protein OmpW was related to salt stress in Vibrio cholerae and that ompW gene transcription and expression were up-regulated in cultures containing high NaCl concentrations. Deletion of ompW resulted in reduced V. cholerae growth in hypersaline culture conditions. Supplements of the compatible solutes betaine, L-carnitine, or L-lysine enhanced the growth of V. cholerae in hypersaline media. Supplements of betaine or L-lysine had the same growth enhancement effect on the ompW-deletion mutant cultured in hypersaline media, whereas L-carnitine supplementation did not restore mutant growth. In addition, the uptake of L-carnitine was decreased in the ompW-deletion mutant. Our study showed that among the multiplex factors that enhance the hypersaline tolerance of V. cholerae, OmpW also plays a role by transporting L-carnitine.

Learning induces the translin/trax RNase complex to express activin receptors for persistent memory.

Long-lasting forms of synaptic plasticity and memory require de novo protein synthesis. Yet, how learning triggers this process to form memory is unclear. Translin/trax is a candidate to drive this learning-induced memory mechanism by suppressing microRNA-mediated translational silencing at activated synapses. We find that mice lacking translin/trax display defects in synaptic tagging, which requires protein synthesis at activated synapses, and long-term memory. Hippocampal samples harvested from these mice following learning show increases in several disease-related microRNAs targeting the activin A receptor type 1C (ACVR1C), a component of the transforming growth factor-ß receptor superfamily. Furthermore, the absence of translin/trax abolishes synaptic upregulation of ACVR1C protein after learning. Finally, synaptic tagging and long-term memory deficits in mice lacking translin/trax are mimicked by ACVR1C inhibition. Thus, we define a new memory mechanism by which learning reverses microRNA-mediated silencing of the novel plasticity protein ACVR1C via translin/trax.