N6-methyladenosine (m6A),catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14,is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However,the roles a...N6-methyladenosine (m6A),catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14,is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However,the roles and precise mechanisms of m6A modification in regulating neuronal development and adult neurogenesis remain unclear. Here,we examined the function of Mettl3,the key component of the complex,in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neu-ronal development and skewed the differentiation of aNSCs more toward glial lineage,but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecip-itation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically,m6A was present on the transcripts of histone methyltransferase Ezh2,and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively,our results uncover a crosstalk between RNA and histone modifica-tions and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.展开更多
The production-oriented approach （POA） has been developed over a decade. It is driven by the need to improve English classroom instruction for university students in China （Wen, 2016）. It is also motivated by the ...The production-oriented approach （POA） has been developed over a decade. It is driven by the need to improve English classroom instruction for university students in China （Wen, 2016）. It is also motivated by the aspiration to enhance the quality of foreign language education in other similar pedagogical contexts outside China. A volume of research has been done by Wen Qiufang and her research team, to formulate the theory of POA and to test its effectiveness in classroom pedagogy （e.g. Wen, 2016, 2015; Yang, 2015; Zhang, 2015）. At the moment, the POA is still at an early stage of theory building and almost all empirical research is done in the Chinese context. In order to improve the quality of this theory and to make it intelligible to the international academic community, a one-day symposium was held in Beijing Foreign Studies University on May 15, 2017. The symposium was entitled ＇The first international forum on innovative foreign language education in China： Appraisal of the POA＇. In the forum, leading experts in applied linguistics were invited to discuss the strengths and weaknesses of the POA and the directions for its future development. The symposium was the first attempt for the POA research team to discuss its latest work with international scholars. This Viewpoint section collects the responses of four experts who participated in the symposium, listed in alphabetical order. The collection of articles covers three topics related to the POA： its pedagogical application, its use for teacher training, and its research. Alister Cumming is Professor Emeritus and the former Head of the Centre for Educational Research on Languages and Literacies, University of Toronto, Canada. His article focuses primarily on POA research as an exemplary case of design-based research. Rod Ellis is Research Professor in the School of Education at Curtin University, Australia. He discusses POA in terms of pedagogy, teacher training and research, with both critiques and constructive suggestions. Paul Kei Matsuda is Professor of English and Director of Second Language Writing at Arizona State University, the writed states. He responds to POA from the perspective of an expert researcher and teacher of L2 writing. Charlene Polio is Professor and Associate Chair in the Department of Linguistics ＆ Germanic, Slavic, Asian ＆ African Languages atMichigan State University, the writed states. She conceptualises POA as a useful method to address some issues in pre-service teacher development. Overall, the articles in this section are insightful and reader-friendly. They are not only useful for the development of POA in particular, but may also be valuable to a broad range of researchers as they touch upon pertaining issues, as well as emerging topics, in the field of applied linguistics. We therefore find it necessary to make them accessible to a wide readership.展开更多
基金supported in part by the International Collaboration Program of the Ministry of Science and Technology of China (Grant No. YS2017YFGH001214)the National Natural Science Foundation of China (Grant Nos. 31771395 and 31571518)+6 种基金the National Key R&D Program of China (Grant No. 2016YFC0900400)supported by the National Natural Science Foundation of China (Grant No. 31770872)the Youth Innovation Promotion Association (Grant No. CAS2018133)the National Key R&D Program of China, Stem Cell and Translational Research (Grant No. 2018YFA0109700)supported in part by the National Key R&D Program of China (Grant No. 2017YFC1001703)the Key R&D Program of Zhejiang Province (Grant No. 2017C03009)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents (2016-6), China
文摘N6-methyladenosine (m6A),catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14,is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However,the roles and precise mechanisms of m6A modification in regulating neuronal development and adult neurogenesis remain unclear. Here,we examined the function of Mettl3,the key component of the complex,in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neu-ronal development and skewed the differentiation of aNSCs more toward glial lineage,but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecip-itation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically,m6A was present on the transcripts of histone methyltransferase Ezh2,and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively,our results uncover a crosstalk between RNA and histone modifica-tions and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.
文摘The production-oriented approach （POA） has been developed over a decade. It is driven by the need to improve English classroom instruction for university students in China （Wen, 2016）. It is also motivated by the aspiration to enhance the quality of foreign language education in other similar pedagogical contexts outside China. A volume of research has been done by Wen Qiufang and her research team, to formulate the theory of POA and to test its effectiveness in classroom pedagogy （e.g. Wen, 2016, 2015; Yang, 2015; Zhang, 2015）. At the moment, the POA is still at an early stage of theory building and almost all empirical research is done in the Chinese context. In order to improve the quality of this theory and to make it intelligible to the international academic community, a one-day symposium was held in Beijing Foreign Studies University on May 15, 2017. The symposium was entitled ＇The first international forum on innovative foreign language education in China： Appraisal of the POA＇. In the forum, leading experts in applied linguistics were invited to discuss the strengths and weaknesses of the POA and the directions for its future development. The symposium was the first attempt for the POA research team to discuss its latest work with international scholars. This Viewpoint section collects the responses of four experts who participated in the symposium, listed in alphabetical order. The collection of articles covers three topics related to the POA： its pedagogical application, its use for teacher training, and its research. Alister Cumming is Professor Emeritus and the former Head of the Centre for Educational Research on Languages and Literacies, University of Toronto, Canada. His article focuses primarily on POA research as an exemplary case of design-based research. Rod Ellis is Research Professor in the School of Education at Curtin University, Australia. He discusses POA in terms of pedagogy, teacher training and research, with both critiques and constructive suggestions. Paul Kei Matsuda is Professor of English and Director of Second Language Writing at Arizona State University, the writed states. He responds to POA from the perspective of an expert researcher and teacher of L2 writing. Charlene Polio is Professor and Associate Chair in the Department of Linguistics ＆ Germanic, Slavic, Asian ＆ African Languages atMichigan State University, the writed states. She conceptualises POA as a useful method to address some issues in pre-service teacher development. Overall, the articles in this section are insightful and reader-friendly. They are not only useful for the development of POA in particular, but may also be valuable to a broad range of researchers as they touch upon pertaining issues, as well as emerging topics, in the field of applied linguistics. We therefore find it necessary to make them accessible to a wide readership.
