The C. elegans Homolog of RBBP6 (RBPL-1) Regulates Fertility through Controlling Cell Proliferation in the Germline and Nutrient Synthesis in the Intestine

Abstract

RBBP6 (retinoblastoma binding protein 6, also known as PACT or P2P-R in humans) is a multi-domain protein that functions in multiple processes, such as mitosis, cell differentiation, and cell apoptosis. RBBP6 is evolutionarily conserved and is present in unicellular organisms to mammals. Studies of RBBP6 have mostly focused on its RB- and p53-binding domains, which are found exclusively in mammals. Here, we investigated the C. elegans homolog of RBBP6 to explore the functional roles of its other domains. We found that RBPL-1, the homolog of RBBP6 in C. elegans, is indispensable for worm development. RNAi silencing of rbpl-1 led to embryonic lethality, as well as defects in oocyte production and intestine development. rbpl-1 RNAi worms showed defects in germ cell proliferation, suggesting that RBPL-1 regulates mitosis. Moreover, RNAi silencing of rbpl-1 inhibited nutrient synthesis in the worm intestine. RBPL-1, as a nucleolus protein, was found to be expressed in diverse tissues and necessary for both germline and soma development. Using microarray analysis, we identified ≈700 genes whose expression levels were changed at least 10-fold in rbpl-1 worms. We propose that RBPL-1, like its yeast homolog, may regulate gene expression as an mRNA cleavage and polyadenylation factor. Taken together, the findings from this study reveal that RBPL-1 plays a pivotal role in C. elegans germline and soma development, suggesting that the functions of RBBP6 are conserved in diverse eukaryotic species.

New genetic regulators question relevance of abundant yolk protein production in C. elegans

“…The initiation of vitellogenesis in Aedes aegypti and Sarcophaga bullata in response to, respectively, a blood or liver meal, is yet another well-known indicator of the existence of such a control mechanism 7 75 76 77 . In C. elegans , other previously identified intestinal vit regulators, such as the lipid metabolism-regulating transcription factor KLF-3 ( K rüppel- l ike f actor (zinc finger protein)) 78 79 and to a lesser extent RBPL-1 ( r etinoblastoma b inding p rotein l ike) 80 , are also possibly involved in the integration of signals regarding the nutritional status of the intestine, i.e. the prime site of lipid metabolism 81 .…”

RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer

“…It promotes the ubiquitination and degradation of p53 protein through its E3 ubiquitin ligase activity. Due to its ability to bind the tumor suppressors p53 and Rb, it has been proposed that RBBP6 plays a key role in cell cycle, cell proliferation, apoptosis and chemoresistance . Knockdown of RBBP6 expression enhanced the chemosensitivity of lung and breast cancer and resulted in the inhibition of tumor growth.…”

ceRNA Networks: The Backbone Role in Neoadjuvant Chemoradiotherapy Resistance/Sensitivity of Locally Advanced Rectal Cancer

“…18 Since retinoblastoma binding protein 6 (RBBP6) demonstrates the capability to bind with the tumor suppressors p53 and Rb, it may be involved in the cell cycle, proliferation, apoptosis, and CRT resistance of tumor cells. [63][64][65] Overexpressed RBBP6 mRNA arrests the G2 to M phase and regulates the apoptosis pathways, which leads to CRT resistance of rectal cancer cells. In contrast, inhibiting cellular RBBP6 expression predisposes rectal tumors to increased CRT sensitivity.…”