ABSTRACT
Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis.
Subject(s)
Cell Differentiation/genetics , Introns/genetics , Meiosis/genetics , Spermatozoa/cytology , Spermatozoa/metabolism , Alternative Splicing/genetics , Animals , Cell Nucleus/genetics , Gene Ontology , Male , Mice, Inbred C57BL , RNA Stability/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Regulatory Sequences, Nucleic Acid/genetics , Spermatogenesis/genetics , Transcription, Genetic , Transcriptome/geneticsABSTRACT
To answer the still unresolved question of the possible leukemogenic effects of extremely low frequency magnetic fields (ELF-MFs) and of their harmonics on the incidence of B acute lymphoblastic leukemia in children, we used an animal model to explore the possible co-initiating or co-promoting effects of ELF-MFs on the development of leukemia. We used a rat model in which B acute lymphoblastic leukemia is chemically induced by a nitrosurea derivative. From the onset of the chemical treatment, the animals were also exposed to ELF-MFs (100 microT, sinusoidal 50 Hz MFs), with or without harmonics. The experiment was conducted on 280 rats. We compared body weight and survival time, percentage of bone marrow blast cells, cumulative incidence of leukemia and type of leukemia in the unexposed groups and in the groups exposed to 50 Hz MFs, with and without harmonics. The results showed no significant differences between exposed and unexposed rats for any of these parameters (p > 0.05). Significant changes in the leukemia type obtained after gamma-irradiation of the leukemia model, showed its sensitivity to a physical agent. Our results do not support the hypothesis that ELF-MFs, with or without harmonics, affect the development of B acute lymphoblastic leukemia in children.
