Dual roles of EGO-1 and RRF-1 in regulating germline exo-RNAi efficiency in Caenorhabditis elegans.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-11 DOI:10.1038/s44319-025-00543-0

Katsufumi Dejima, Keita Yoshida, Shohei Mitani

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引用次数: 0

Abstract

RNA interference (RNAi) is widely used in life science research and is critical for diverse biological processes, such as germline development and antiviral defense. In the germline of Caenorhabditis elegans, exogenous RNAi (exo-RNAi), the RNA-dependent RNA polymerases EGO-1 and RRF-1 play redundant roles in facilitating small RNA amplification. However, their coordination during the regulation of exo-RNAi processes in the germline remains unclear. Here, we examine non-null mutants of the ego-1 gene and find that ego-1(S1198L) animals exhibit germline exo-RNAi defects with normal fertility, abnormalities in germ granules, and synthetic temperature-dependent sterility with rrf-1. The exo-RNAi defects in ego-1(S1198L) are partially restored by inhibiting hrde-1 and znfx-1. Germline exo-RNAi defects are observed in wild-type and ego-1(S1198L) heterozygous descendants derived from ego-1(S1198L), but these are suppressed by ancestral inhibition of rrf-1. Our data reveal a dual role for EGO-1 in the positive regulation of germline exo-RNAi: it not only mediates target silencing through its RNA-dependent RNA polymerase activity, but also licenses exo-RNAi gene expression, which is antagonized by RRF-1.

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EGO-1和RRF-1在秀丽隐杆线虫种系外rnai效率调控中的双重作用

RNA干扰（RNA interference, RNAi）广泛应用于生命科学研究，在多种生物过程中起着至关重要的作用，如生殖细胞发育和抗病毒防御。在秀丽隐杆线虫种系中，外源性RNAi （exo-RNAi）、RNA依赖的RNA聚合酶EGO-1和RRF-1在促进小RNA扩增中发挥了冗余作用。然而，它们在种系外链rnai过程调控中的协调作用尚不清楚。在这里，我们研究了ego-1基因的非零突变体，发现ego-1（S1198L）动物表现出生殖系外显rnai缺陷，具有正常的生育能力，胚粒异常，以及rrf-1的合成温度依赖性不育。通过抑制hrde-1和znfx-1，可以部分恢复ego-1（S1198L）的外显rnai缺陷。在野生型和由ego-1（S1198L）衍生的ego-1（S1198L）杂合后代中观察到种系外rnai缺陷，但这些缺陷被祖先对rrf-1的抑制所抑制。我们的数据揭示了EGO-1在种系外显子rnai阳性调控中的双重作用：它不仅通过其RNA依赖的RNA聚合酶活性介导靶标沉默，而且还允许外显子rnai基因表达，这是由RRF-1拮抗的。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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