Autophagy is an intracellular degradation system that is present in most eukaryotes. In the process of autophagy, double membrane vesicles called autophagosomes sequester a wide variety of cellular constituents and deliver them to lytic organelles: lysosomes in mammals and vacuoles in yeast and plants. Although autophagy used to be considered a non-selective process in its target sequestration into autophagosomes, recent studies have revealed that autophagosomes can also selectively sequester certain proteins and organelles that have become unnecessary or harmful for the cell. We recently discovered that the endoplasmic reticulum (ER) is degraded by autophagy in a selective manner in the budding yeast Saccharomyces cerevisiae, and identified “receptor proteins” that play pivotal roles in this “ER-phagy” pathway. Moreover, several ER-phagy receptors in mammalian cells have also been reported. This report provides an overview of our current knowledge on ER-phagy and discuss their mechanisms, physiological roles, and possible links to human diseases.

Forward genetics is a powerful approach to understand the molecular basis of animal behaviors. Fruit flies were the first animal to which this genetic approach was applied systematically and have provided major discoveries on behaviors including sexual, learning, circadian, and sleep-like behaviors. The development of different classes of model organism such as nematodes, zebrafish, and mice has enabled genetic research to be conducted using more-suitable organisms. The unprecedented success of forward genetic approaches was the identification of the transcription–translation negative feedback loop composed of clock genes as a fundamental and conserved mechanism of circadian rhythm. This approach has now expanded to sleep/wakefulness in mice. A conventional strategy such as dominant and recessive screenings can be modified with advances in DNA sequencing and genome editing technologies.

RNA silencing refers to gene silencing pathways mediated by small non-coding RNAs, including microRNAs. Piwi-interacting RNAs (piRNAs) constitute the largest class of small non-coding RNAs in animal gonads, which repress transposons to protect the germline genome from the selfish invasion of transposons. Deterioration of the system causes DNA damage, leading to severe defects in gametogenesis and infertility. Studies using Drosophila ovaries show that piRNAs originate from specific genomic loci, termed piRNA clusters, and that in piRNA biogenesis, cluster transcripts are processed into mature piRNAs via three distinct pathways: initiator or responder for ping-pong piRNAs and trailing for phased piRNAs. piRNAs then assemble with PIWI members of the Argonaute family of proteins to form piRNA-induced RNA silencing complexes (piRISCs), the core engine of the piRNA-mediated silencing pathway. Upon piRISC assembly, the PIWI member, Piwi, is translocated to the nucleus and represses transposons co-transcriptionally by inducing local heterochromatin formation at target transposon loci.