生物
核糖核酸
外显子
RNA编辑
RNA沉默
RNA剪接
非编码RNA
内含子
遗传学
小核RNA
转录后修饰
细胞生物学
RNA干扰
基因
作者
Rei Yoshimoto,Yuta Nakayama,I. Nomura,Ikuko Yamamoto,Yûzô Nakagawa,Shigeyuki Tanaka,Misuzu Kurihara,Y. Suzuki,Takehiko Kobayashi,Hiroko Kozuka‐Hata,Masaaki Oyama,Mari Mito,Shigeo Iwasaki,T. Yamazaki,Tetsuro Hirose,Kimi Araki,Shinichi Nakagawa
标识
DOI:10.1016/j.molcel.2023.11.019
摘要
4.5SH RNA is a highly abundant, small rodent-specific noncoding RNA that localizes to nuclear speckles enriched in pre-mRNA-splicing regulators. To investigate the physiological functions of 4.5SH RNA, we have created mutant mice that lack the expression of 4.5SH RNA. The mutant mice exhibited embryonic lethality, suggesting that 4.5SH RNA is an essential species-specific noncoding RNA in mice. RNA-sequencing analyses revealed that 4.5SH RNA protects the transcriptome from abnormal exonizations of the antisense insertions of the retrotransposon SINE B1 (asB1), which would otherwise introduce deleterious premature stop codons or frameshift mutations. Mechanistically, 4.5SH RNA base pairs with complementary asB1-containing exons via the target recognition region and recruits effector proteins including Hnrnpm via its 5′ stem loop region. The modular organization of 4.5SH RNA allows us to engineer a programmable splicing regulator to induce the skipping of target exons of interest. Our results also suggest the general existence of splicing regulatory noncoding RNAs.
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