LIN28B

LIN28B 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. This gene is highly expressed in testis, fetal liver, placenta, and in primary human tumors and cancer cell lines. LIN28B 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. Diseases associated with LIN28B include Idiopathic Central Precocious Puberty and Oral Cavity Cancer. Among its related pathways are Translational Control and Validated targets of C-MYC transcriptional activation.

Full Name

LIN28B

Function

Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA (PubMed:22118463).
Does not act on pri-miR21 (PubMed:22118463).
The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation (PubMed:19703396).
This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent (PubMed:22118463).
Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression (By similarity).
When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.

Biological Process

miRNA catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of pre-miRNA processingManual Assertion Based On ExperimentIDA:CACAO
Negative regulation of primary miRNA processingManual Assertion Based On ExperimentIDA:CACAO
Positive regulation of miRNA catabolic processManual Assertion Based On ExperimentIMP:CACAO
Pre-miRNA processingManual Assertion Based On ExperimentIMP:UniProtKB
RNA 3'-end processingManual Assertion Based On ExperimentIMP:UniProtKB
RNA destabilizationManual Assertion Based On ExperimentIDA:CACAO

Cellular Location

Nucleus
Nucleus, nucleolus
Cytoplasm
Predominantly nucleolar (PubMed:22118463).
In Huh7 cells, predominantly cytoplasmic, with only a subset of cells exhibiting strong nuclear staining; however, the specificity of the polyclonal antibody used in these experiments has not been not documented (PubMed:16971064).