YTH Domain Containing 1 (YTHDC1) is one of the m6A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating m6A reader YTHDC1 may provide a potential therapeutic target for ischemic stroke.

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Capsaicinoids are naturally specialized metabolites in pepper and are the main reason that Capsicum fruits have a pungent smell. During the synthesis of capsaicin, MYB transcription factors play key regulatory roles. In particular, R2R3-MYB subfamily genes are the most important members of the MYB family and are critical candidate factors in capsaicinoid biosynthesis. The 108 R2R3-MYB genes in pepper were identified in this study and all are shown to have two highly conserved MYB binding domains. Phylogenetic and structural analyses clustered CaR2R3-MYB genes into seven groups. Interspecies collinearity analysis found that the R2R3-MYB family contains 16 duplicated gene pairs and the highest gene density is on chromosome 00 and 03. The expression levels of CaR2R3-MYB differentially expressed genes (DEGs) and capsaicinoid-biosynthetic genes (CBGs) in fruit development stages were obtained via RNA-seq and quantitative polymerase chain reaction (qRT-PCR). Co-expression analyses reveal that highly expressed CaR2R3-MYB genes are co-expressed with CBGs during early stages of pericarp and placenta development processes. It is speculated that six candidate CaR2R3-MYB genes are involved in regulating the synthesis of capsaicin and dihydrocapsaicin. This study is the first systematic analysis of the CaR2R3-MYB gene family and provided references for studying their molecular functions. At the same time, these results also laid the foundation for further research on the capsaicin characteristics of CaR2R3-MYB genes in pepper.

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To detect syntaxin-binding protein 1 (STXBP1) mutations in Chinese patients with early onset epileptic encephalopathy (EOEE) of unknown etiology. Targeted next-generation sequencing was used to identify STXBP1 mutations in 143 Chinese patients with EOEE of unknown etiology. A filtering process was applied to prioritize rare variants of potential functional significance. Then Sanger sequencing was employed to validate the parental origin of the variants. Detailed clinical and genetic data were collected for 9 STXBP1-positive patients. Eight de novo heterozygous STXBP1 mutations were identified in 9 patients; 5 were novel mutations (c.1155delC, c.1030-1G>A, c.217G>C, c.268G>C, c.1480_1481 insT) and 3 were previously reported (c.1216C> T, c.1217G>A [2 cases], c.875G>A). Two patients had Ohtahara syndrome and 1 had West syndrome at onset, whereas the other 6 presented with EOEE that did not fit a specific recognized epilepsy syndrome. Six of these patients later evolved to West syndrome. All but 2 cases were prescribed more than 2 antiepileptic drugs (AEDs) plus other regimens. Four subjects showed good responses to levetiracetam (LEV) alone or in combination with other AEDs, and one case (1/3) achieved complete freedom from seizures with a ketogenic diet (KD). All patients exhibited severe to profound global developmental delay. Five novel heterozygous de novo STXBP1 mutations were discovered in patients with EOEE from China. STXBP1 mutational analysis should be performed in cases of EOEE of unknown etiology. LEV as monotherapy or adjunctive therapy with other regimens, as well as KD should be considered for management of this patient group.

Background Synonymous mutations do not change the protein sequences. Automatically, they have been regarded as neutral events and are ignored in the mutation-based cancer studies. However, synonymous mutations will change the codon optimality, resulting in altered translational velocity. Methods We fully utilized the transcriptome and translatome of liver cancer and normal tissue from ten patients. We profiled the mutation spectrum and examined the effect of synonymous mutations on translational velocity. Results Synonymous mutations that increase the codon optimality significantly enhanced the translational velocity, and were enriched in oncogenes. Meanwhile, synonymous mutations decreasing codon optimality slowed down translation, and were enriched in tumor suppressor genes. These synonymous mutations significantly contributed to the translational changes in tumor samples compared to normal samples. Conclusions Synonymous mutations might play a role in liver cancer development by altering codon optimality and translational velocity. Synonymous mutations should no longer be ignored in the genome-wide studies.

Mitochondrial transcription termination factors (mTERFs) regulate the expression of mitochondrial genes and are closely related to the function of the mitochondrion and chloroplast. In this study, the mTERF gene family in capsicum (Capsicum annuum L.) was identified and characterized through genomic and bioinformatic analyses. Capsicum was found to possess at least 35 mTERF genes (CamTERFs), which were divided into eight major groups following phylogenetic analysis. Analysis of CamTERF promoters revealed the presence of many cis-elements related to the regulation of cellular respiration and photosynthesis. In addition, CamTERF promoters contained cis-elements related to phytohormone regulation and stress responses. Differentially expressed genes in different tissues and developmental phases were identified using RNA-seq data, which revealed that CamTERFs exhibit various expression and co-expression patterns. Gene ontology (GO) annotations associated CamTERFs primarily with mitochondrion and chloroplast function and composition. These results contribute towards understanding the role of mTERFs in capsicum growth, development, and stress responses. Moreover, our data assist in the identification of CamTERFs with important functions, which opens avenues for future studies.

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