Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation.
Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation.
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DOI：
10.1038/s41598-017-17407-w
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发表时间：
2017-12-12
影响因子：
4.6
通讯作者：
Martin KC
中科院分区：
文献类型：
--
作者：
Fontes MM;Guvenek A;Kawaguchi R;Zheng D;Huang A;Ho VM;Chen PB;Liu X;O'Dell TJ;Coppola G;Tian B;Martin KC
作为学习和记忆基础的突触可塑性的持久形式需要新的转录和翻译才能持久。神经元的显著极性和区分性提出了关于神经元内基因表达的时空调控的问题。交替切割和多聚腺苷酸化(APA)产生具有不同3‘非翻译区(3’UTRs)和/或编码序列的mRNA异构体。MRNAs的3‘非编码区组成的变化可以通过调节转录的定位、稳定性和/或翻译来改变基因的表达，而编码序列的变化导致mRNAs编码不同的蛋白质。我们采用专门的3‘端深度测序方法，对小鼠海马CA3-CA1突触长时程增强(LTP)诱导后的APA进行了全面的分析。我们发现了LTP诱导的APA的广泛变化，包括3‘非编码区缩短和内含子APA亚型激活的总趋势。与转录组的比较表明，大多数APA调控事件与转录丰度的变化无关。我们进一步表明，特定的APA调控事件可以影响LTP过程中两个已知功能的分子的表达，包括Notch1的3‘UTRAPA和Creb1的内含子APA。综上所述，我们的结果表明，活性依赖的APA在学习和记忆过程中提供了一个重要的基因调节层。
Long-lasting forms of synaptic plasticity that underlie learning and memory require new transcription and translation for their persistence. The remarkable polarity and compartmentalization of neurons raises questions about the spatial and temporal regulation of gene expression within neurons. Alternative cleavage and polyadenylation (APA) generates mRNA isoforms with different 3′ untranslated regions (3′UTRs) and/or coding sequences. Changes in the 3′UTR composition of mRNAs can alter gene expression by regulating transcript localization, stability and/or translation, while changes in the coding sequences lead to mRNAs encoding distinct proteins. Using specialized 3′ end deep sequencing methods, we undertook a comprehensive analysis of APA following induction of long-term potentiation (LTP) of mouse hippocampal CA3-CA1 synapses. We identified extensive LTP-induced APA changes, including a general trend of 3′UTR shortening and activation of intronic APA isoforms. Comparison with transcriptome profiling indicated that most APA regulatory events were uncoupled from changes in transcript abundance. We further show that specific APA regulatory events can impact expression of two molecules with known functions during LTP, including 3′UTR APA of Notch1 and intronic APA of Creb1. Together, our results reveal that activity-dependent APA provides an important layer of gene regulation during learning and memory.
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影响因子：
19
作者：
Buxbaum AR;Yoon YJ;Singer RH;Park HY
通讯作者：
Park HY
影响因子：
16
作者：
Fischl H;Howe FS;Furger A;Mellor J
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Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
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Greenberg, Michael E.
Notch1通过与Reelin通路、谷氨酸能传递和CREB信号相互作用调控海马可塑性
影响因子：
5.3
作者：
Brai E;Marathe S;Astori S;Fredj NB;Perry E;Lamy C;Scotti A;Alberi L
通讯作者：
Alberi L
影响因子：
64.5
作者：
Berg, Michael G.;Singh, Larry N.;Dreyfuss, Gideon
通讯作者：
Dreyfuss, Gideon