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The ribonuclease DIS3 promotes let-7 miRNA maturation by degrading the pluripotency factor LIN28B mRNA.

Segalla S, Pivetti S, Todoerti K, Chudzik MA, Giuliani EC, Lazzaro F, Volta V, Lazarevic D, Musco G, Muzi-Falconi M, Neri A, Biffo S, Tonon G - Nucleic Acids Res. (2015)

Bottom Line: DIS3 facilitates the maturation of let-7 miRNAs by reducing in the cytoplasm the RNA stability of the pluripotency factor LIN28B, a inhibitor of let-7 processing.DIS3 inactivation, through the increase of LIN28B and the reduction of mature let-7, enhances the translation of let-7 targets such as MYC and RAS leading to enhanced tumorigenesis.Our study establishes that the ribonuclease DIS3, targeting LIN28B, sustains the maturation of let-7 miRNAs and suggests the increased translation of critical oncogenes as one of the biological outcomes of DIS3 inactivation.

View Article: PubMed Central - PubMed

Affiliation: Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, 20133 Milan, Italy.

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DIS3 controls let-7 through LIN28B. LIN28B mRNA (left panel) and let-7-a and let-7-g (right panel) levels of one representative experiment in which RPMI cells infected with a scrambled shRNA (ctrl) or with a DIS3 shRNA4 (DIS3 sh) underwent, after 3 days, a second infection with a scrambled shRNA (ctrl) or with a LIN28B shRNA. LIN28B and let-7 levels were measured 4 days after the second infection and normalized over GAPDH and RNU6B respectively. Bars represent SDs (n = 2 replicas of one representative experiment).
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Figure 5: DIS3 controls let-7 through LIN28B. LIN28B mRNA (left panel) and let-7-a and let-7-g (right panel) levels of one representative experiment in which RPMI cells infected with a scrambled shRNA (ctrl) or with a DIS3 shRNA4 (DIS3 sh) underwent, after 3 days, a second infection with a scrambled shRNA (ctrl) or with a LIN28B shRNA. LIN28B and let-7 levels were measured 4 days after the second infection and normalized over GAPDH and RNU6B respectively. Bars represent SDs (n = 2 replicas of one representative experiment).

Mentions: To conclusively demonstrate that LIN28B is required for the repression of let-7 as a result of DIS3 knockdown, the concomitant silencing of LIN28B and DIS3 was carried out in RPMI and U2OS cells (Figure 5 and Supplementary Figures S10 and S11). We found that in both cell lines knockdown of LIN28B completely abrogated the reduction of mature let-7 mediated by DIS3 silencing, confirming that LIN28B is required for DIS3-mediated let-7 reduction (Figure 5 and Supplementary Figure S11, right panel).


The ribonuclease DIS3 promotes let-7 miRNA maturation by degrading the pluripotency factor LIN28B mRNA.

Segalla S, Pivetti S, Todoerti K, Chudzik MA, Giuliani EC, Lazzaro F, Volta V, Lazarevic D, Musco G, Muzi-Falconi M, Neri A, Biffo S, Tonon G - Nucleic Acids Res. (2015)

DIS3 controls let-7 through LIN28B. LIN28B mRNA (left panel) and let-7-a and let-7-g (right panel) levels of one representative experiment in which RPMI cells infected with a scrambled shRNA (ctrl) or with a DIS3 shRNA4 (DIS3 sh) underwent, after 3 days, a second infection with a scrambled shRNA (ctrl) or with a LIN28B shRNA. LIN28B and let-7 levels were measured 4 days after the second infection and normalized over GAPDH and RNU6B respectively. Bars represent SDs (n = 2 replicas of one representative experiment).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 5: DIS3 controls let-7 through LIN28B. LIN28B mRNA (left panel) and let-7-a and let-7-g (right panel) levels of one representative experiment in which RPMI cells infected with a scrambled shRNA (ctrl) or with a DIS3 shRNA4 (DIS3 sh) underwent, after 3 days, a second infection with a scrambled shRNA (ctrl) or with a LIN28B shRNA. LIN28B and let-7 levels were measured 4 days after the second infection and normalized over GAPDH and RNU6B respectively. Bars represent SDs (n = 2 replicas of one representative experiment).
Mentions: To conclusively demonstrate that LIN28B is required for the repression of let-7 as a result of DIS3 knockdown, the concomitant silencing of LIN28B and DIS3 was carried out in RPMI and U2OS cells (Figure 5 and Supplementary Figures S10 and S11). We found that in both cell lines knockdown of LIN28B completely abrogated the reduction of mature let-7 mediated by DIS3 silencing, confirming that LIN28B is required for DIS3-mediated let-7 reduction (Figure 5 and Supplementary Figure S11, right panel).

Bottom Line: DIS3 facilitates the maturation of let-7 miRNAs by reducing in the cytoplasm the RNA stability of the pluripotency factor LIN28B, a inhibitor of let-7 processing.DIS3 inactivation, through the increase of LIN28B and the reduction of mature let-7, enhances the translation of let-7 targets such as MYC and RAS leading to enhanced tumorigenesis.Our study establishes that the ribonuclease DIS3, targeting LIN28B, sustains the maturation of let-7 miRNAs and suggests the increased translation of critical oncogenes as one of the biological outcomes of DIS3 inactivation.

View Article: PubMed Central - PubMed

Affiliation: Functional Genomics of Cancer Unit, Division of Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, 20133 Milan, Italy.

Show MeSH
Related in: MedlinePlus