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Pereirinha, J.

Publications and source records attributed to Pereirinha, J..

3 recordsLinked to original sources

SLBP-independent control of maternal histone mRNA

Replication-dependent (RD) histones are crucial for packaging newly replicated DNA into chromatin, ensuring genome stability. In metazoans, the mRNA of RD histones is uniquely regulated through a conserved 3' stem-loop bound by stem-loop binding protein (SLBP). This allows cell cycle-coupled regulation of these important transcripts. However, oocytes must stabilise histone mRNAs independently of the cell cycle to ensure maternal loading to support the first embryonic divisions. Using Caenorhabditis elegans as a model system, we discovered an SLBP-independent mechanism that ensures RD histone transcript stability during oogenesis. This is mediated by the protein complex PETISCO, bound to the effector protein TOST-1, which directly binds the histone stem-loop region and maintains maternal histone mRNA levels during oogenesis and early embryogenesis. Loss of this mechanism disrupts histone homeostasis, leading to premature genome activation, mitotic defects, and embryonic lethality. Interestingly, the same complex, PETISCO, acts in piRNA biogenesis when bound to the effector PID-1, revealing an intriguing co-option of this histone mRNA homeostasis mechanism by the piRNA pathway. Our findings reveal a unique SLBP-independent mechanism of histone mRNA regulation, that served as a basis for the evolution of a novel piRNA biogenesis mechanism.

molecular biology↗

Neurogenetic evidence for oscillatory behavior of Lgr3-positive growth control interneurons in Drosophila

The ability to achieve a species-specific size and proportion despite developmental or environmental perturbations is termed developmental stability. The molecular and cellular processes behind this are best understood in insects. In Drosophila, a peripheral-tissue stress signal, the relaxin/insulin-like peptide Dilp8, promotes developmental stability during larval development via its neuronal receptor, Lgr3, an ortholog of vertebrate relaxin receptors. Lgr3 signaling is widely accepted to occur in-and to activate (depolarize)-the central brain growth-coordinating interneurons (PIL/GCL neurons). Here, using neurogenetic approaches, we confirm the requirement of Lgr3 in PIL/GCL neurons, but unexpectedly find that they require both silenced (hyperpolarized) and active (depolarized) states for an appropriate response to Dilp8. These results are most simply explained if Lgr3 activation by Dilp8 triggers PIL/GCL-neuron oscillatory activity, and such oscillations promote developmental stability. PIL/GCL neurons express and require Cyclin A-which can form cell-cycle oscillator complexes with cyclin-dependent kinases-for their response to Dilp8, independently of Rca1 (regulator of CycA)/Emi1 (early mitotic inhibitor). This opens the possibility that cell-cycle machinery can be co-opted for postmitotic neuron oscillations, adding to an increasing list of postmitotic roles for cyclins. Neuroanatomically, we show that PIL/GCL neurons form reciprocally-innervating loops, which are common architectures in oscillating circuits and central pattern generators. The role of PIL/GCL neurons in developmental stability mirrors other homeostasis-regulating, peptide-driven oscillatory circuits found in the vertebrate hypothalamus, a developmentally-homologous region to the one occupied by PIL/GCL neurons in the fly brain.

neuroscience↗

Innate behavior sequence progression by peptide-mediated interorgan crosstalk

Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of fly larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling.

animal behavior and cognition↗