The Ancient Source of a Distinct Gene Family Encoding Proteins Featuring RING and C3H Zinc-Finger Motifs with Abundant Expression in Developing Brain and Nervous System
Abstract
Intronless genes can arise by germline retrotransposition of a cDNA originating as mRNA from an intron-containing source gene. Previously, we described several members of a family of intronless mammalian genes encoding a novel class of zinc-finger proteins, including one that shows imprinted expression and one that escapes X-inactivation. We report here the identification and characterization of the Makorin ring finger protein 1 gene (MKRN1), a highly transcribed, intron-containing source for this family of genes. Phylogenetic analyses clearly indicate that the MKRN1 gene is the ancestral founder of this gene family. We have identified MKRN1 orthologs from human, mouse, wallaby, chicken, fruitfly, and nematode, underscoring the age and conservation of this gene. The MKRN gene family encodes putative ribonucleoproteins with a distinctive array of zinc-finger motifs, including two to four C(3)H zinc-fingers, an unusual Cys/His arrangement that may represent a novel zinc-finger structure, and a highly conserved RING zinc-finger. To date, we have identified nine MKRN family loci distributed throughout the human genome. The human and mouse MKRN1 loci map to a conserved syntenic group near the T-cell receptor beta cluster (TCRB) in chromosome 7q34-q35 and chromosome 6A, respectively. MKRN1 is widely transcribed in mammals, with high levels in murine embryonic nervous system and adult testis. The ancient origin of MKRN1, high degree of conservation, and expression pattern suggest important developmental and functional roles for this gene and its expressed family members.
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MKRN3 belongs to the Makorin family, a family of E3 ubiquitin ligases.
“MKRN3 belongs to the Makorin family, a family of E3 ubiquitin ligases.78”
From Pubertal development and regulation (2016) · cites this paper as [78]
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Differentiation linked regulation of telomerase activity by Makorin-1
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Regulation of Apoptosis During Porcine Circovirus Type 2 Infection
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MRKNs: Gene, Functions, and Role in Disease and Infection
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Copy number variation in pediatric multiple sclerosis
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MKRN1 Ubiquitylates p21 to Protect against Intermittent Hypoxia‐Induced Myocardial Apoptosis
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Cellular Source of the Poxviral N1R/p28 Gene Family
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- Authors
- Gray, T. A., Hernandez, L., Carey, A. H., Schaldach, M. A., Smithwick, M. J., Rus, K., Marshall Graves, J. A., Stewart, C. L., & Nicholls, R. D.
- Affiliations
- University Hospitals of Cleveland (US)
- Frederick National Laboratory for Cancer Research (US)
- La Trobe University (AU)
- John Carroll University (US)
- Corresponding author
- Nicholls, Robert D.
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 66
- Issue
- 1
- Pages
- 76-86
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W2133978355
- Cited by
- 108
- References
- 37
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 9 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 5
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd036079-06)
- National Institute of General Medical Sciences (GM18306, F32GM018306)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD31491, R01HD031491, HD36079)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- MKRN1, gene family evolution, zinc finger proteins, intronless genes, phylogenetic analysis, ribonucleoprotein, brain development, testis expression, syntenic groups, chromosome 6A, X-inactivation escape
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Brain, Cytogenetics, Drosophila, Embryo, Mammalian, Embryo, Nonmammalian, Exons, Multigene Family, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Nervous System, Phylogeny, Ribonucleoproteins, RNA, Messenger, Tissue Distribution, Zinc Fingers, Sequence Alignment, Sequence Analysis, DNA, DNA, Complementary, Gene Expression Regulation, Developmental, Evolution, Molecular, Expressed Sequence Tags, Amino Acid Motifs, Gene Expression Profiling, Mice
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