Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR.
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR
J Cell Biol. 2018 Feb 5;217(2):541-553. doi: 10.1083/jcb.201707082. Epub 2017 Dec 29.
Mammalian cells replicate their chromosomes via a temporal replication program. The and genes were identified as loci that when disrupted result in delayed replication and condensation of entire human chromosomes. ASAR6 and ASAR15 are monoallelically expressed long noncoding RNAs that remain associated with the chromosome from which they are transcribed. The chromosome-wide effects of map to the antisense strand of an L1 retrotransposon within ASAR6 RNA, deletion or inversion of which delayed replication of human chromosome 6. Furthermore, ectopic integration of or transgenes into mouse chromosomes resulted in delayed replication and condensation, an increase in H3K27me3, coating of the mouse chromosome with ASAR RNA, and a loss of mouse Cot-1 RNA expression in cis. Targeting the antisense strand of the L1 within ectopically expressed ASAR6 RNA restored normal replication timing. Our results provide direct evidence that L1 antisense RNA plays a functional role in chromosome-wide replication timing of mammalian chromosomes.
哺乳动物细胞通过一个时间性的复制程序来复制其染色体。和 基因被鉴定为位置，当它们被破坏时，会导致整个人类染色体的复制延迟和浓缩。ASAR6 和 ASAR15 是单等位基因表达的长非编码 RNA，它们与转录它们的染色体保持关联。的染色体-wide 效应映射到 ASAR6 RNA 中的一个 L1 反转录转座子的反义链上，缺失或倒位会延迟人类染色体 6 的复制。此外，或 转基因的异位整合到小鼠染色体上会导致复制延迟和浓缩，H3K27me3 的增加，ASAR RNA 对小鼠染色体的覆盖，以及顺式 Cot-1 RNA 表达的丢失。针对异位表达的 ASAR6 RNA 中的 L1 反义链，恢复了正常的复制时间。我们的结果提供了直接的证据，表明 L1 反义 RNA 在哺乳动物染色体的全染色体复制时间中起着功能性作用。
