A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment

Rybak, Agnieszka; Fuchs, Heiko; Smirnova, Lena; Brandt, Christine; Pohl, Elena E.; Nitsch, Robert; Wulczyn, F. Gregory

doi:10.1038/ncb1759

Cited by 736 publications

(748 citation statements)

References 33 publications

Supporting

Mentioning

713

Contrasting

Unclassified

Order By: Relevance

“…More intriguingly, the MYC was posttranscriptionally regulated by let-7, but it can also control the expression of let-7 (or other miRNAs) at the level of transcription through repressing RNA polymerase-II to prevent pri-let-7 RNA transcription (Sampson et al, 2007;Chang et al, 2008). Similar to MYC, LIN28, as a target of let-7, can also prevent either pri-let-7 and/or pre-let-7 from processing mature let-7 in murine embryonic stem cells and undifferentiated cancer stem cells (Rybak et al, 2008). Consequently, let-7, MYC and LIN28 interact to make an autoregulatory feedback loop (Figure 4).…”

Section: Microrna and Metastasis H Zhang Et Almentioning

confidence: 99%

The microRNA network and tumor metastasis

2009

View full text Add to dashboard Cite

Metastasis is the most significant process affecting the clinical management of cancer patients and occurs in multiple sequential steps. However, the molecular pathways underlying each step still remain obscure. Recent research has shown that there is a microRNA (miRNA) network that functions as a regulator of tumor metastasis. In this paper, we review the role of miRNAs in tumor metastasis, including control of epithelial-mesenchymal transition, regulation of metastasis-associated genes and epigenetic alterations. More information on miRNAs will promote a better understanding of the molecular mechanism of metastasis.

show abstract

Section: Microrna and Metastasis H Zhang Et Almentioning

confidence: 99%

The microRNA network and tumor metastasis

2009

View full text Add to dashboard Cite

show abstract

“…It has been shown to block the processing of let-7 microRNAs (Heo et al, 2008;Newman et al, 2008;Rybak et al, 2008;Viswanathan et al, 2008) as well as a handful of other microRNAs (Heo et al, 2009;Trabucchi et al, 2009). In addition, Lin28 has been reported by us and others to bind to a specific subset of mRNAs, including those for IGF-2, Oct4, and several cell cycle-related factors, thereby modulating their translation (Polesskaya et al, 2007;Qiu et al, 2009;.…”

Section: Introductionmentioning

confidence: 99%

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

2010

View full text Add to dashboard Cite

“…One more motif in the tuning mode is shown in Figure 1C. In the study of Rybak et al (2008), the human miRNA, let-7, forms a double-negative feedback loop with the mammalian homolog of locus lin-28 in Caenorhabditis elegans. The expression of lin-28 determines the pluripotency of the embryonic stem cells.…”

Section: The Dual Functions Of Mirnas-expression Tuning and Expressiomentioning

confidence: 99%

Evolution under canalization and the dual roles of microRNAs—A hypothesis

Wu¹,

Shen²,

Tang³

2009

Genome Res.

146

160

View full text Add to dashboard Cite

Canalization refers to the process by which phenotypes are stabilized within species. Evolution by natural selection can proceed efficiently only when phenotypes are canalized. The existence and identity of canalizing genes have thus been an important, but controversial topic. Recent evidence has increasingly hinted that microRNAs may be involved in canalizing gene expression. Their paradoxical properties (e.g., strongly conserved but functionally dispensable) suggest unconventional regulatory roles. We synthesized published and unpublished results and hypothesize that miRNAs may have dual functions-in gene expression tuning and in expression buffering. In tuning, miRNAs modify the mean expression level of their targets, but in buffering they merely reduce the variance around a preset mean. In light of the constant emergence of new miRNAs, we further discuss the relative importance of these two functions in evolution.Living organisms process as much information and execute as many instructions as any high-power computers normally do. The difference is that living organisms carry out the tasks under extremely variable environments, whereas no computers are made to withstand even moderate fluctuations in voltage input. Living things must be able to dampen variable inputs (in nutrition, temperature, humidity, genetic background, etc.) to achieve the remarkable stability in the output (development, physiological responses, gene expression, etc.). This phenomenon is the essence of biological homeostasis.Darwin's The Origin of Species (Darwin 1859), on the other hand, is about evolutionary changes. On the surface, evolutionary changes and phenotypic stability may seem like antithetical concepts, but in the language of genetics they are really two sides of the same issue. Evolution by natural selection can proceed only when biological systems are reasonably stable. Imagine a system in which phenotypic manifestation is highly variable. In it natural selection cannot easily distinguish one genotype from another and would have low efficacy. The original nongenetic version of the Darwinian theory encountered many difficulties. One of them was the blending of genetic materials, potentially leading to the homogenization of phenotypes. The other resulted from the ignorance of the difference between genotype and phenotype and the puzzle over the existence of phenotypic variation. Fisher (1930) pointed out that, in Darwin's thinking, phenotypic variation should have been purged by natural selection-only the fittest should have remained.The relationship between evolution and biological homeostasis can best be expressed in quantitative genetic terms. Let V g and V e denote phenotypic variance due to genotypic and environmental effect, respectively. V g 3 e is the interactive term between gene and environment. The total phenotypic variance, V t , can be expressed as follows:For simplicity, we assume no dominance here, but the general principle is the same in more complex systems. Any mechanism of biological homeostasis should redu...

show abstract

A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment

Cited by 736 publications

References 33 publications

The microRNA network and tumor metastasis

The microRNA network and tumor metastasis

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

Evolution under canalization and the dual roles of microRNAs—A hypothesis

Contact Info

Product

Resources

About