Non-coding RNAs enter mitosis: functions, conservation and implications

Abstract

Nuage (or commonly known as chromatoid body in mammals) is a conserved germline-specific organelle that has been linked to the Piwi-interacting RNA (piRNA) pathway. piRNAs are a class of gonadal-specific RNAs that are ~23-29 nucleotides in length and protect genome stability by repressing the expression of deleterious retrotransposons. More recent studies in Drosophila have implicated the piRNA pathway in other functions including canalization of embryonic development, regulation of maternal gene expression and telomere protection. We have recently shown that Vasa (known as Mouse Vasa Homolog in mouse), a nuage component, plays a mitotic role in promoting chromosome condensation and segregation by facilitating robust chromosomal localization of condensin I in the Drosophila germline. Vasa functions together with Aubergine (a PIWI family protein) and Spindle-E/mouse TDRD-9, two other nuage components that are involved in the piRNA pathway, therefore providing a link between the piRNA pathway and mitotic chromosome condensation. Here, we propose and discuss possible models for the role of Vasa and the piRNA pathway during mitosis. We also highlight relevant studies implicating mitotic roles for RNAs and/or nuage in other model systems and their implications for cancer development.

Figure 1

The dynamic localization of Vasa during mitosis in Drosophila germline stem cells. During interphase and prophase, Vasa (green) localizes as peri-nuclear bodies in the cytoplasm (nuage). When the nuclear envelope (dark blue line) begins to break down during prometaphase, Vasa gets access to the chromosomes (red) and localizes as peri-chromosomal bodies. This continues until metaphase. At anaphase, some Vasa bodies remain near segregation chromosomes, while the other bodies are displaced in between the segregating sister chromatids. NC: nucleus, Vas: Vasa.

Figure 2

Proposed mechanisms by which Vasa regulates condensin I (CAP-H) localization. (A) The Recruitment model: Vasa functions primarily to recruit CAP-H at the peri-centromeric regions. After CAP-H loading, it spreads to the distal chromosome arms. (B) The Stabilization model: At the peri-centromeric region, Vasa functions in a yet unknown mechanism to promote a stable association of CAP-H to the mitotic chromosomes. Aub: Aubergine, Spn-E: Spindle-E,