Me31B: a key repressor in germline regulation and beyond

Abstract

Maternally Expressed at 31B (Me31B), an evolutionarily conserved ATP-dependent RNA helicase, plays an important role in the development of the germline across diverse animal species. Its cellular functionality has been posited as a translational repressor, participating in various RNA metabolism pathways to intricately regulate the spatiotemporal expression of RNAs. Despite its evident significance, the precise role and mechanistic underpinnings of Me31B remain insufficiently understood. This article endeavors to comprehensively review historic and recent research on Me31B, distill the major findings, discern generalizable patterns in Me31B's functions across different research contexts, and provide insights into its fundamental role and mechanism of action. The primary focus of this article centers on elucidating the role of Drosophila Me31B within the germline, while concurrently delving into pertinent research on its orthologs within other species and cellular systems.

Keywords: Germ granules; Germline; Me31B; Neuronal granules; RNA helicase; Ribonucleoprotein (RNP).

Figure 1. Drosophila oogenesis and Me31B expression in the egg chambers

Me31B-GFP expression is visualized in an ovariole expressing GFP-tagged wild-type Me31B [19]. The top image is a sketch outlining the egg chambers and nurse cells while the bottom image shows Me31B-GFP observed using confocal microscopy.

Figure 2. The model of a Me31B complex in germline RNP

In this model of Me31B-containing RNP, the Me31B protein assumes a pivotal role as the central hub, orchestrating interactions with four groups of protein partners: RNA regulators, cytoskeleton/motor proteins, glycolytic enzymes, and core germ plasm proteins. Among these, the RNA regulators, including Me31B itself, provide post-transcriptional RNA regulations. Cytoskeleton/motor proteins facilitate the transportation of the RNP. Glycolytic enzymes contribute ATP resources to power the activities of other proteins within the assembly. Lastly, core germ plasm proteins play integral roles in the assembly of germ plasm/nuage and the formation of germ cells. The figure is adapted from DeHaan et al. [40].

Figure 3. The model of a Me31B-containing repressor complex on nos mRNA

The model involves Smaug (Smg), functioning as an RNA repressor/degrader, binding to Smaug Recognition Elements (SREs) in the 3′ UTR of nos during embryonic Maternal to Zygotic Transition (MTZ). Smg recruits Cup, which then interacts with eIF4E, Tral, and Me31B. Multiple Me31B-Tral complexes coat nos RNA, hindering translation. Additionally, Me31B or eIF4E may also engage Belle (Bel) to further suppress nos RNA. Finally, Me31B and/or Smaug recruit the CCR4-NOT deadenylation complex, leading to nos RNA degradation. The figure is adapted from Gotze et al. [54].

Figure 4. A schematic illustration of the mechanisms of how Me31B affects target mRNAs

In this model, Me31B shows various ways of influencing its target mRNA. First, it oligomerizes and coats the mRNA, functioning as a general repressor. Second, it cooperates with RISC, a small RNA-equipped mRNA silencing machinery, in mRNA degradation/repression. Third, Me31B collaborates with decapping factors (Decapper) to facilitate mRNA decapping. Additionally, it physically interacts with CCR4-NOT complex, which induces mRNA deadenylation. Finally, Me31B may directly interact with ribosomes, impeding mRNA translation. Notably, these interconnected mechanisms of action may operate independently or synergistically in a unified RNA regulation pathway.