Biology subjects

Perez, G. I.

Publications and source records attributed to Perez, G. I..

2 recordsLinked to original sources

bioRxiv2021

In vitro and in vivo analysis of microvesicle-mediated metastasis using a bright, red-shifted bioluminescent reporter protein of extracellular vesicles

Cancer cells produce heterogeneous extracellular vesicles (EVs) as mediators of intercellular communication. Our study focused on a novel method to image EV subtypes and their biodistribution in vivo. Regardless of injection routes, we established that reporter EVs isolated from murine mammary carcinoma cells expressing PalmReNL, which utilizes bioluminescence resonance energy transfer (BRET), localized to the lungs. This new EV reporter allowed highly sensitive EV tracking in vitro and in vivo and enabled us to begin studies to understand the commonalities and functional differences of the EV subtypes. We demonstrated the early appearance of metastatic foci in the lungs of mammary tumor-bearing mice following multiple injections of the microvesicle (MV)-enriched fraction derived from mammary carcinoma cells. In addition, the results we present here show that tumor cell-derived MVs act on distant tissues through upregulating LC3 expression within the lung.

cancer biology↗

bioRxiv2021

TCAB1 is necessary for telomerase assembly

Localization of a wide variety of RNAs to non-membrane bound cellular compartments such as nucleoli, Cajal bodies, and stress-granules is critical for their function and stability. The molecular mechanisms that underly the recruitment and exclusion of specific RNAs from these phase-separated organelles is incompletely understood. Telomerase is a ribonucleoprotein (RNP) that is composed of the reverse transcriptase protein TERT, the telomerase RNA (TR), and several auxiliary proteins that associate with TR, including TCAB1. Here we show that in the absence of TCAB1, TR is tightly bound to the nucleolus, while TERT localizes to the nucleoplasm and is largely excluded from the nucleolus, significantly reducing telomerase assembly. Thus, nuclear compartmentalization by the non-membrane bound nucleolus counteracts telomerase assembly and TCAB1 is required to exclude the telomerase RNA from the nucleolus. Our work provides insight into the mechanism and functional consequences of RNA recruitment to organelles formed by phase separation proposes a new model explaining the critical role of TCAB1 in telomerase function.

cell biology↗