LIN28B

Lin-28 homolog B is a protein that in humans is encoded by the LIN28B gene.^[5] Lin28 is a gene found in both invertebrates and vertebrates, from worms to humans, where it regulates the timing of development from fertilization to adulthood.^[6][7][8]

LIN28B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4A4I
Identifiers
Aliases	LIN28B, CSDD2, lin-28 homolog B
External IDs	OMIM: 611044; MGI: 3584032; HomoloGene: 47607; GeneCards: LIN28B; OMA:LIN28B - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q16.3-q21 Start 104,936,616 bp[1] End 105,083,332 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 B2 Start 45,252,716 bp[2] End 45,362,491 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in placenta buccal mucosa cell gonad testicle secondary oocyte sperm decidua Brodmann area 23 right testis left testis Top expressed in tail of embryo zygote secondary oocyte embryo embryo primary oocyte genital tubercle spermatocyte epiblast morula More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding zinc ion binding protein binding metal ion binding RNA binding nucleic acid binding Cellular component cytoplasm nucleus nucleolus cytosol Biological process pre-miRNA processing miRNA catabolic process gene silencing regulation of transcription, DNA-templated RNA 3'-end processing Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 389421 380669 Ensembl ENSG00000187772 ENSMUSG00000063804 UniProt Q6ZN17 Q45KJ6 RefSeq (mRNA) NM_001004317 NM_001031772 NM_001033152 RefSeq (protein) NP_001004317 NP_001026942 Location (UCSC) Chr 6: 104.94 – 105.08 Mb Chr 10: 45.25 – 45.36 Mb PubMed search [3] [4]
Wikidata
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Evolution

Lin28B can be traced to a mutational event that occurred around 300 million years ago during which a large section of a heterochronic gene, Lin28, now referred to as Lin28A, was duplicated resulting in the appearance of a paralog, Lin28B.^[6][7][8]

Structure

The protein encoded by this gene belongs to the lin-28 family, which is characterized by the presence of a cold-shock domain and a pair of CCHC zinc finger domains.

Tissue distribution

This gene is highly expressed in testis, fetal liver, placenta, and in primary human tumors and cancer cell lines.

Function

LIN28B is an evolutionarily conserved RNA-binding protein primarily known for its role in regulating the maturation of let-7 microRNAs, which are important for cell differentiation and development. During embryogenesis and in stem cells, LIN28B blocks differentiation and promotes cell proliferation by inhibiting let-7 biogenesis, thereby preventing the accumulation of these tumor-suppressive miRNAs. Mechanistically, the N-terminal cold-shock domain (CSD) and the C-terminal zinc-knuckle domain (ZKD) of LIN28B allow for stepwise binding to immature let-7 pre-miRNAs, triggering their remodeling and subsequent uridylation and degradation, effectively silencing their functions.^[9][10][11]

developmental timing, pluripotency, and tumorigenesis, chiefly by controlling miRNA biogenesis and acting as an RNA-binding protein, but it also possesses let-7–independent roles in direct gene regulation and cellular metabolism.^[10]

Clinical significance

It is negatively regulated by microRNAs that target sites in the 3' UTR, and overexpression of this gene in primary tumors is linked to the repression of let-7 family of microRNAs and derepression of let-7 targets, which facilitates cellular transformation.

Even minor changes in Lin28 are known to alter the timing of developmental stages and thereby affect all features that emerge during those stages.^[6][7] The duplication shifted the developmental clock backward, such that mammals carrying both Lin28A and Lin28B gave birth earlier in gestation.^[12][13] As a result, mammalian offspring were born less developed, requiring greater maternal investment. This innovation marked the appearance of mammals and accounts for two of their distinguishing features compared to reptiles and amphibians: altricial young and increased maternal bonding.^[14]