No abstract

Pre-RNA splicing is an essential step in generating mature mRNA. RNA trans-splicing combines two separate pre-mRNA molecules to form a chimeric non-co-linear RNA, which may exert a function distinct from its original molecules. Trans-spliced RNAs may encode novel proteins or serve as noncoding or regulatory RNAs. These novel RNAs not only increase the complexity of the proteome but also provide new regulatory mechanisms for gene expression. An increasing amount of evidence indicates that trans-splicing occurs frequently in both physiological and pathological processes. In addition, mRNA reprogramming based on trans-splicing has been successfully applied in RNA-based therapies for human genetic diseases. Nevertheless, clarifying the extent and evolution of trans-splicing in vertebrates and developing detection methods for trans-splicing remain challenging. In this review, we summarize previous research, highlight recent advances in trans-splicing, and discuss possible splicing mechanisms and functions from an evolutionary viewpoint.

SOX9 transcription factor is involved in chondrocyte differentiation and male sex determination. Heterozygous defects in the human SOX9 gene cause campomelic dysplasia. The mechanisms behind SOX9 function are not understood despite the description of different target genes. This study therefore sets out to identify SOX9-associated proteins to unravel how SOX9 interacts with the cellular transcription machinery. We report the ability of SOX9 to interact with TRAP230, a component of the thyroid hormone receptor-associated protein (TRAP) complex. Both in vitro and in vivo assays have confirmed that the detected interaction is specific and occurs endogenously in cells. Using co-transfection experiments, we have also shown that the TRAP230 interacting domain can act in a dominant-negative manner regarding SOX9 activity. Our results add SOX9 to the list of activators that communicate with the general transcription machinery through the TRAP complex and suggest a basis for the collaboration of SOX9 with different coactivators that could contact the same coactivator/integrator complex.

Macroautophagy/autophagy is a catabolic process that is essential for cellular homeostasis. Studies on autophagic degradation of cytoplasmic components have generated interest in nuclear autophagy. Although its mechanisms and roles have remained elusive, tremendous progress has been made toward understanding nuclear autophagy. Nuclear autophagy is evolutionarily conserved in eukaryotes that may target various nuclear components through a series of processes, including nuclear sensing, nuclear export, autophagic substrate encapsulation and autophagic degradation in the cytoplasm. However, the molecular processes and regulatory mechanisms involved in nuclear autophagy remain largely unknown. Numerous studies have highlighted the importance of nuclear autophagy in physiological and pathological processes such as cancer. This review focuses on current advances in nuclear autophagy and provides a summary of its research history and landmark discoveries to offer new perspectives.

The Sox9 gene encodes a transcription factor that is critical for testis determination and chondrogenesis in vertebrates. Mutations in human SOX9 cause campomelic dysplasia, a dominant skeletal dysmorphology syndrome often associated with male to female sex reversal. Here we show that the Sox9a gene was duplicated during evolution of the rice field eel, Monopterus albus, a freshwater fish which undergoes natural sex reversal from female to male during its life, and has a haploid genome size (0.6-0.8 pg) that is among the smallest of the vertebrates. The duplicated copies of the gene (named Sox9al and Sox9a2) fit within the Sox9 clade of vertebrates, especially in the Sox9a subfamily, not in the Sox9b subfamily. They have similar structures as revealed by both genomic and cDNA analysis. Furthermore, both Sox9al and Sox9a2 are expressed in testis, ovary, and ovotestis; and specifically in the outer layer (mainly gonocytes) of gonadal epithelium with bipotential capacity to form testis or ovary, suggesting that they have similar roles in gonadal differentiation during sex reversal in this species. The closely related gene structure and expression patterns of the two sox9a genes in the rice field eel also suggest that they arose in recent gene duplication events during evolution of this fish lineage.