Biology subjects

Ichiyanagi, K.

Publications and source records attributed to Ichiyanagi, K..

3 recordsLinked to original sources

bioRxiv2024

Birth of protein-coding exons by ancient domestication of LINE retrotransposon

Transposons, occasionally domesticated as novel host protein-coding genes, are responsible for the lineage-specific functions in vertebrates. LINE-1 (L1) is one of the most active transposons in the vertebrate genomes. Despite its abundance, the contribution of L1 to the birth of vertebrate proteins remains unelucidated. Here, we present a novel mechanism for the origination of de novo proteins, in which the L1 retrotransposons are incorporated into host genes as protein-coding exons by alternative splicing. L1 ORF1 protein (ORF1p) is an RNA-binding protein that binds to L1 RNA and is required for retrotransposition by acting as an RNA chaperone. We identified a splicing variant of myosin light chain 4 (MYL4) containing an L1 ORF1-derived exon and encoding a chimeric protein of L1 ORF1p and MYL4, named Lyosin. Molecular evolutionary analysis revealed that Lyosin was acquired in the common ancestor of reptiles and birds during the Paleozoic era. The amino acid sequence of Lyosin had undergone purifying selection although it was lost in some lineages, including the Neognathae birds and snakes. The transcripts encoding Lyosin were expressed in the testes of two lizard species, suggesting that its function is different from that of the canonical MYL4 expressed specifically in the heart. Furthermore, sequence searches revealed other evolutionarily conserved chimeric isoforms fused to the L1 ORF1p in three genes in vertebrates. Our findings suggest a novel evolutionary mechanism for the birth of lineage-specific proteins derived from transposons and implicate the previously unrecognized adaptive functions of L1 ORF1p.

evolutionary biology↗

bioRxiv2021

Transcriptional states of retroelement-inserted regions and KRAB zinc finger protein association regulate DNA methylation of retroelements in human male germ cells

DNA methylation, repressive histone modifications, and PIWI-interacting RNAs are essential for controlling retroelement silencing in mammalian germ lines. Dysregulation of retroelement silencing is associated with male sterility. Although retroelement silencing mechanisms have been extensively studied in mouse germ cells, little progress has been made in humans. Here, we show that the Kruppel-associated box domain zinc finger proteins (KRAB-ZFPs) are associated with DNA methylation of retroelements in human primordial germ cells (hPGCs), and hominoid-specific retroelement SINE-VNTR-Alus (SVA) is subjected to transcription-directed de novo DNA methylation during human spermatogenesis. Furthermore, we show that the degree of de novo DNA methylation in SVAs varies among human individuals, which confers a significant inter-individual epigenetic variation in sperm. Collectively, our results provide potential molecular mechanisms for the regulation of retroelements in human male germ cells.

molecular biology↗

bioRxiv2020

Heritable endogenization of an RNA virus in a mammalian species

Viruses are considered one of the driving forces for genome rearrangements via infection and endogenization into the host genome (Kazazian, 2004; Maksakova et al., 2006). In 2010, Horie and colleagues demonstrated that a non-retroviral RNA virus, Borna disease virus (BDV), could integrate into the genome in cultured somatic cells (Horie et al., 2010). However, germline transmission of viral-derived sequences using animal models is yet to be experimentally demonstrated. In this study, we reported a case of heritable endogenization using the encephalomyocarditis virus (EMCV) and laboratory mice. The EMCV is a small non-enveloped single-strand RNA virus without its own reverse transcriptase activity (Carocci et al., 2012). Here, we demonstrated that the EMCV genomic RNA was reverse transcribed into DNA fragments in the murine testes. The DNA sequence originated from the RNA genome of EMCV was also detected in the liver and earlobes of the offspring generated from the EMCV-infected father. This suggests that the exogenous sequence derived from the EMCV is transmitted into the host germline and inherited across subsequent generations. This first experimental demonstration of viral endogenization proposes reconsideration about the impact of viruses as a driving force for genome modification.

genetics↗