Sandbox Reserved 718: Difference between revisions

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The other domain has the binding element AAGNNG (most frequent sequence: AAGGAG) which can be found downstream of the GNGAY motif. The first G builds a hydrogen bond with <scene name='Sandbox_Reserved_718/Lys160/2'>LYS160</scene>  in the zinc finger motif. <ref>Jun Cho, Hyeshik Chang, S. Chul Kwon, Baekgyu Kim, Yoosik Kim, Junho Choe, Minju Ha, Yoon Ki Kim, and V. Narry Kim: ''Lin28A Is a Suppressor of ER-Associated Translation in Embryonic Stem Cells.'' In: Cell 151, S.765–777, November 9, 2012</ref>
The other domain has the binding element AAGNNG (most frequent sequence: AAGGAG) which can be found downstream of the GNGAY motif. The first G builds a hydrogen bond with <scene name='Sandbox_Reserved_718/Lys160/2'>LYS160</scene>  in the zinc finger motif. <ref>Jun Cho, Hyeshik Chang, S. Chul Kwon, Baekgyu Kim, Yoosik Kim, Junho Choe, Minju Ha, Yoon Ki Kim, and V. Narry Kim: ''Lin28A Is a Suppressor of ER-Associated Translation in Embryonic Stem Cells.'' In: Cell 151, S.765–777, November 9, 2012</ref>


When lin28A interacts with let-7(main target), they build a complex with a crystallographic structure together.
<Structure load='2li8' size='300' frame='true' align='right' caption='pdb 2li8 crystall structure lin28A/let-7' scene='Sandbox_Reserved_718/Lin28a_let-7/1' />
When lin28A interacts with <scene name='Sandbox_Reserved_718/Let-7/1'>let-7</scene>(main target), they build a complex with a crystallographic structure together.


== '''Activity''' ==
== '''Activity''' ==
<Structure load='2li8' size='300' frame='true' align='right' caption='pdb 2li8 crystall structure lin28A/let-7' scene='Sandbox_Reserved_718/Lin28a_let-7/1' />
At the molecular level, Lin28 acts as a suppressor of let-7 microRNA biogenesis.<ref>Heo, I., Joo, C., Cho, J., Ha, M., Han, J., and Kim, V.N. In: ''Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.'' Mol. Cell 32, S.276–284, 2008.</ref><ref>Newman, M.A., Thomson, J.M., and Hammond, S.M. In: ''Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing.'' RNA 14, 1539–1549, 2008.</ref><ref>Rybak, A., Fuchs, H., Smirnova, L., Brandt, C., Pohl, E.E., Nitsch, R., and Wulczyn, F.G. In: ''A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment.'' Nat. Cell Biol. 10, S.987–993, 2008.</ref><ref>Viswanathan, S.R., Daley, G.Q., and Gregory, R.I. In: ''Selective blockade of microRNA processing by Lin28.'' Science 320, 97–100, 2008.</ref> In the nucleus, Lin28 binds to the primary transcript of let-7 (pri-let-7) and prevents its processing by RNase III DROSHA.<ref>Newman, M.A., Thomson, J.M., and Hammond, S.M. In: ''Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing.'' RNA 14, 1539–1549, 2008.</ref><ref>Viswanathan, S.R., Daley, G.Q., and Gregory, R.I. In: ''Selective blockade of microRNA processing by Lin28.'' Science 320, 97–100, 2008.</ref> In the cytoplasm, it interacts with the precursor form of let-7 (pre-let-7) and interferes with pre-let-7 processing. <ref>Heo, I., Joo, C., Cho, J., Ha, M., Han, J., and Kim, V.N. In: ''Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.'' Mol. Cell 32, S.276–284, 2008.</ref><ref>Rybak, A., Fuchs, H., Smirnova, L., Brandt, C., Pohl, E.E., Nitsch, R., and Wulczyn, F.G. In: ''A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment.'' Nat. Cell Biol. 10, S.987–993, 2008.</ref> Lin28 recruits TUTase 4 (ZCCHC11) to induce oligo-uridylation of pre-let-7, which effectively blocks DICER processing and facilitates degradation of the RNA. <ref>Hagan, J.P., Piskounova, E., and Gregory, R.I. In: ''Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells.'' Nat. Struct. Mol. Biol. 16, S.1021–1025, 2009.</ref><ref>Heo, I., Joo, C., Cho, J., Ha, M., Han, J., and Kim, V.N. In: ''Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.'' Mol. Cell 32, S.276–284, 2008.</ref><ref>Heo, I., Joo, C., Kim, Y.K., Ha, M., Yoon, M.J., Cho, J., Yeom, K.H., Han, J., and Kim, V.N. In: ''TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.'' Cell 138, S.696–708, 2009.</ref> Lin28A is found mostly in the cytoplasmic compartment and acts in concert with TUTase 4.<ref>Piskounova, E., Polytarchou, C., Thornton, J.E., LaPierre, R.J., Pothoulakis, C., Hagan, J.P., Iliopoulos, D., and Gregory, R.I. In: ''Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.'' Cell 147, S.1066–1079, 2011.</ref>
At the molecular level, Lin28 acts as a suppressor of let-7 microRNA biogenesis.<ref>Heo, I., Joo, C., Cho, J., Ha, M., Han, J., and Kim, V.N. In: ''Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.'' Mol. Cell 32, S.276–284, 2008.</ref><ref>Newman, M.A., Thomson, J.M., and Hammond, S.M. In: ''Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing.'' RNA 14, 1539–1549, 2008.</ref><ref>Rybak, A., Fuchs, H., Smirnova, L., Brandt, C., Pohl, E.E., Nitsch, R., and Wulczyn, F.G. In: ''A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment.'' Nat. Cell Biol. 10, S.987–993, 2008.</ref><ref>Viswanathan, S.R., Daley, G.Q., and Gregory, R.I. In: ''Selective blockade of microRNA processing by Lin28.'' Science 320, 97–100, 2008.</ref> In the nucleus, Lin28 binds to the primary transcript of let-7 (pri-let-7) and prevents its processing by RNase III DROSHA.<ref>Newman, M.A., Thomson, J.M., and Hammond, S.M. In: ''Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing.'' RNA 14, 1539–1549, 2008.</ref><ref>Viswanathan, S.R., Daley, G.Q., and Gregory, R.I. In: ''Selective blockade of microRNA processing by Lin28.'' Science 320, 97–100, 2008.</ref> In the cytoplasm, it interacts with the precursor form of let-7 (pre-let-7) and interferes with pre-let-7 processing. <ref>Heo, I., Joo, C., Cho, J., Ha, M., Han, J., and Kim, V.N. In: ''Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.'' Mol. Cell 32, S.276–284, 2008.</ref><ref>Rybak, A., Fuchs, H., Smirnova, L., Brandt, C., Pohl, E.E., Nitsch, R., and Wulczyn, F.G. In: ''A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment.'' Nat. Cell Biol. 10, S.987–993, 2008.</ref> Lin28 recruits TUTase 4 (ZCCHC11) to induce oligo-uridylation of pre-let-7, which effectively blocks DICER processing and facilitates degradation of the RNA. <ref>Hagan, J.P., Piskounova, E., and Gregory, R.I. In: ''Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells.'' Nat. Struct. Mol. Biol. 16, S.1021–1025, 2009.</ref><ref>Heo, I., Joo, C., Cho, J., Ha, M., Han, J., and Kim, V.N. In: ''Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.'' Mol. Cell 32, S.276–284, 2008.</ref><ref>Heo, I., Joo, C., Kim, Y.K., Ha, M., Yoon, M.J., Cho, J., Yeom, K.H., Han, J., and Kim, V.N. In: ''TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.'' Cell 138, S.696–708, 2009.</ref> Lin28A is found mostly in the cytoplasmic compartment and acts in concert with TUTase 4.<ref>Piskounova, E., Polytarchou, C., Thornton, J.E., LaPierre, R.J., Pothoulakis, C., Hagan, J.P., Iliopoulos, D., and Gregory, R.I. In: ''Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.'' Cell 147, S.1066–1079, 2011.</ref>


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Katrin Frohnmüller, Teresa Wiese
Katrin Frohnmüller, Teresa Wiese
/ref
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