An Important Role of Pumilio 1 in Regulating the Development of the Mammalian Female Germline1

Abstract

Pumilio/FBF (PUF) proteins are a highly conserved family of translational regulators. The Drosophila PUF protein, Pumilio, is crucial for germline establishment and fertility. In mammals, primordial folliculogenesis is a key process that establishes the initial cohort of female mammalian germ cells prior to birth, and this primordial follicle pool is a prerequisite for female reproductive competence. We sought to understand whether PUF proteins have a conserved role in mammals during primordial folliculogenesis and female reproductive competency. In mammals, two homologs of Pumilio exist: Pumilio 1 (Pum1) and Pum2. Here, we report that PUMILIO (PUM) 1 plays an important role in the establishment of the primordial follicle pool, meiosis, and female reproductive competency, whereas PUM2 does not have a detectable function in these processes. Furthermore, we show that PUM1 facilitates the transition of the late meiotic prophase I oocyte from pachytene to diplotene stage by regulating SYCP1 protein. Our study reveals an important role of translational regulation in mammalian female germ cell development.

Unique repression domains of Pumilio utilize deadenylation and decapping factors to accelerate destruction of target mRNAs

“…Indeed, as noted above, accumulating evidence supports the role of deadenylation, decapping, and translational inhibition in Pum repression in multiple model organisms. Mammalian Pum orthologs have crucial, diverse roles in growth and development, gametogenesis, hematopoiesis, neurogenesis, behavior, motor function and memory formation (97)(98)(99)(100)(101)(102)(103)(104)(105)(106). Their dysfunction has now been linked to cancer, neurodegeneration, epilepsy, memory impairment, reduced fertility, and developmental defects in mammals (97,98,100,103,(107)(108)(109)(110)(111).…”

ELAVL2‐directed RNA regulatory network drives the formation of quiescent primordial follicles

“…Traditionally, studies on reproductive biology have documented integral contributions of post‐transcriptional RNA regulation mediated by species‐specific and evolutionarily conserved RNA‐binding proteins (RBPs) to oocyte development . Consistent with this, many important processes of mammalian oogenesis, including sexual differentiation and meiosis in embryonic ovaries, and oocyte growth or maturation in postnatal ovaries, require the functions of RBPs . However, the role of post‐transcriptional RNA regulation in primordial follicle formation remains unknown.…”

Human PUM1 and PUM2 exhibit regulation of divergent mRNA targets in male germ cells

“…A number of PUM protein cofactors such as NANOS1, NANOS3 and DAZ family members are associated with male or female infertility in humans (Jaruzelska, Kotecki et al, 2003, Kusz-Zamelczyk, Sajek et al, 2013, Moore, Jaruzelska et al, 2003, Reijo, Lee et al, 1995, Santos, Machado et al, 2014. Also PUM1 itself was found to be important for male and female fertility (Chen, Zheng et al, 2012, Mak, Fang et al, 2016, Xu, Chang et al, 2007.…”