Alternative titles; symbols
HGNC Approved Gene Symbol: MIRLET7B
Cytogenetic location: 22q13.31 Genomic coordinates (GRCh38): 22:46,113,686-46,113,768 (from NCBI)
MicroRNAs (miRNAs) are small noncoding regulatory RNAs that downregulate transcription by targeting specific mRNAs. Let7, one of the founding members of the miRNA family, was first identified in C. elegans. There are several human homologs of C. elegans let7, and all of these LET7 miRNAs share an identical seed sequence critical for target recognition. Among the human LET7 miRNAs, LET7B and LET7E (611250) are most divergent, with differences in 4 nucleotides. In human, mouse, and C. elegans, expression of LET7 is barely detectable in embryonic stages, but it increases after differentiation and in mature tissues (Lee and Dutta, 2007). For further information on LET7, see LET7A1 (605386).
Using a directional cloning procedure to clone miRNAs from HeLa cell total RNA, Lagos-Quintana et al. (2001) identified 9 human homologs of C. elegans let7, including LET7B. The LET7B sequence is UGAGGUAGUAGGUUGUGUGGUU.
Using database analysis, luciferase reporter assays, and mutagenesis, Lee and Dutta (2007) identified 6 functional LET7 target sites in the 3-prime UTR of HMGA2 (600698). Combined ectopic expression of LET7B and LET7E, which the authors used to represent all LET7 miRNAs, reduced HMGA2 expression and cell proliferation in a lung cancer cell line. In contrast, inhibition of LET7 induced HMGA2 mRNA and protein. Overexpression of the HMGA2 ORF without the 3-prime UTR rescued the growth-suppressive effect of LET7 on lung cancer cells.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas acute myeloid leukemia (AML; 601626) is the most common acute leukemia in adults. Using genomewide mRNA expression analysis, Mi et al. (2007) identified LET7B as an miRNA downregulated in ALL compared with AML. Real-time PCR confirmed downregulation of LET7B in ALL samples compared with AML samples and normal controls.
Selbach et al. (2008) used a proteomic approach, SILAC ('stable-isotope labeling with amino acids in cell culture'), to measure changes in synthesis of several thousand proteins in response to miRNA transfection or endogenous miRNA knockdown. In parallel, they quantified mRNA levels using microarrays. They studied the effect of reducing expression of LET7B in HeLa cells. Other analyses studied the effects of miRNA overexpression in HeLa cells. Their data indicated that upregulation and downregulation of stationary LET7B levels has largely complementary effects on the proteome, with LET7B levels having the potential to tune protein production from thousands of genes. Selbach et al. (2008) observed that Dicer (606241), which has several LET7 3-prime UTR seeds critical for target recognition, was one of the most strongly upregulated genes in the LET7B knockdown SILAC, but not in the microarray data. Therefore, they considered Dicer likely to be a direct translational target of LET7B. This raised the possibility that LET7B can regulate mature mRNA levels.
By genomic sequence analysis, Lagos-Quintana et al. (2001) mapped the MIRNLET7B gene to chromosome 22, 938 nucleotides from the MIRNLET7A3 gene (612143). Mi et al. (2007) stated that the MIRNLET7B gene maps to chromosome 22q13.
Lagos-Quintana, M., Rauhut, R., Lendeckel, W., Tuschl, T. Identification of novel genes coding for small expressed RNAs. Science 294: 853-858, 2001. [PubMed: 11679670] [Full Text: https://doi.org/10.1126/science.1064921]
Lee, Y. S., Dutta, A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 21: 1025-1030, 2007. [PubMed: 17437991] [Full Text: https://doi.org/10.1101/gad.1540407]
Mi, S., Lu, J., Sun, M., Li, Z., Zhang, H., Neilly, M. B., Wang, Y., Qian, Z., Jin, J., Zhang, Y., Bohlander, S. K., Le Beau, M. M., Larson, R. A., Golub, T. R., Rowley, J. D., Chen, J. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc. Nat. Acad. Sci. 104: 19971-19976, 2007. [PubMed: 18056805] [Full Text: https://doi.org/10.1073/pnas.0709313104]
Selbach, M., Schwanhausser, B., Thierfelder, N., Fang, Z., Khanin, R., Rajewsky, N. Widespread changes in protein synthesis induced by microRNAs. Nature 455: 58-63, 2008. [PubMed: 18668040] [Full Text: https://doi.org/10.1038/nature07228]