Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development.
Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development.
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DOI：
10.1371/journal.pgen.1007412
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发表时间：
2018-05
期刊：
影响因子：
4.5
通讯作者：
Wang PJ
中科院分区：
文献类型：
--
作者：
Kasowitz SD;Ma J;Anderson SJ;Leu NA;Xu Y;Gregory BD;Schultz RM;Wang PJ
n6 -甲基腺苷（m6A）修饰是真核生物中最常见的内部RNA修饰。大多数m6A位点位于最后外显子和3 ' utr。在这里，我们表明核m6A读取器YTHDC1对小鼠胚胎活力和种系发育至关重要。具体来说，YTHDC1是男性精原细胞发育和女性卵母细胞生长和成熟所必需的；缺乏ythdc1的卵母细胞在初级卵泡期被阻断。引人注目的是，YTHDC1的缺失导致卵母细胞中广泛的选择性聚腺苷化，改变3 ' UTR长度。此外，YTHDC1缺乏导致卵母细胞中大量的选择性剪接缺陷。突变卵母细胞中的大多数剪接缺陷通过引入野生型而不是m6a结合缺陷的YTHDC1来修复。YTHDC1与mrna前3 '端加工因子CPSF6、SRSF3和SRSF7相关。因此，YTHDC1在卵母细胞核前mrna转录物的加工中起关键作用，并可能在胎儿发育过程中发挥类似的非冗余作用。n6 -甲基腺苷（m6A）修饰是真核信使RNA中最丰富的内部RNA修饰，是RNA甲基化的一种。m6A被rna结合解读蛋白特异性识别。在这里，我们报道了核m6A读取器YTHDC1在胚胎发育和生育中的重要作用。特别是，YTHDC1是卵母细胞生长和成熟所必需的。缺乏YTHDC1的卵母细胞在选择性剪接中表现出大量缺陷，这可以通过引入野生型的突变卵母细胞来挽救，但不能通过引入m6a结合缺陷的YTHDC1来挽救。引人注目的是，YTHDC1的缺失导致卵母细胞中广泛的选择性聚腺苷化，导致3 ' UTR长度改变。YTHDC1与mrna前3 '端加工因子CPSF6、SRSF3和SRSF7相互作用。因此，YTHDC1是mrna前转录物加工过程中的关键核因子。
The N6-methyladenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotes. The majority of m6A sites are found in the last exon and 3’ UTRs. Here we show that the nuclear m6A reader YTHDC1 is essential for embryo viability and germline development in mouse. Specifically, YTHDC1 is required for spermatogonial development in males and for oocyte growth and maturation in females; Ythdc1-deficient oocytes are blocked at the primary follicle stage. Strikingly, loss of YTHDC1 leads to extensive alternative polyadenylation in oocytes, altering 3’ UTR length. Furthermore, YTHDC1 deficiency causes massive alternative splicing defects in oocytes. The majority of splicing defects in mutant oocytes are rescued by introducing wild-type, but not m6A-binding-deficient, YTHDC1. YTHDC1 is associated with the pre-mRNA 3’ end processing factors CPSF6, SRSF3, and SRSF7. Thus, YTHDC1 plays a critical role in processing of pre-mRNA transcripts in the oocyte nucleus and may have similar non-redundant roles throughout fetal development. The N6-methyladenosine (m6A) modification, one type of RNA methylation, is the most abundant internal RNA modification in eukaryote messenger RNAs. m6A is specifically recognized by RNA-binding reader proteins. Here we report an essential role of the nuclear m6A reader, YTHDC1, in embryo development and fertility. In particular, YTHDC1 is required for oocyte growth and maturation. YTHDC1-deficient oocytes exhibit massive defects in alternative splicing, which can be rescued by introducing into mutant oocytes wild-type, but not m6A-binding-deficient, YTHDC1. Strikingly, loss of YTHDC1 causes extensive alternative polyadenylation in oocytes, resulting in altered 3’ UTR length. YTHDC1 interacts with the pre-mRNA 3’end processing factors CPSF6, SRSF3, and SRSF7. Thus, YTHDC1 is a key nuclear factor in the processing of pre-mRNA transcripts.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
16.6
作者：
Abby E;Tourpin S;Ribeiro J;Daniel K;Messiaen S;Moison D;Guerquin J;Gaillard JC;Armengaud J;Langa F;Toth A;Martini E;Livera G
通讯作者：
Livera G
影响因子：
14.9
作者：
Clancy, MJ;Shambaugh, ME;Bokar, JA
通讯作者：
Bokar, JA
影响因子：
5.3
作者：
CAMPER, SA;ALBERS, RJ;ROTTMAN, FM
通讯作者：
ROTTMAN, FM
影响因子：
1.5
作者：
Gallardo, Teresa;Shirley, Lane;Castrillon, Diego H.
通讯作者：
Castrillon, Diego H.