Sandbox Reserved 718: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
Line 6: Line 6:
<scene name='Sandbox_Reserved_718/Lin28a/1'>lin28A</scene>
<scene name='Sandbox_Reserved_718/Lin28a/1'>lin28A</scene>


== '''Activity''' ==
== '''Description''' ==
Lin28 is a conserved cytoplasmic protein with an unusual pairing of RNA binding motifs: a cold shock domain and a pair of retroviral type CCHC zinc fingers. It plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, Lin28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. Mammals have two homologs, Lin28a and Lin28b. These two homologs are found from worms to humans.<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><ref>Erica Balzer and Eric G. Moss: ''Localization of the Developmental Timing Regulator Lin28 to mRNP Complexes, P-bodies and Stress Granules.'' In: RNA Biology 4:1, S.16-25, January/February/March 2007.</ref> Lin28a is highly expressed in embryonic stem cells (ESCs) and was shown as one of the four factors that convert fibroblasts into induced pluripotent stem cells.<ref>Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., et al. In: ''Induced pluripotent stem cell lines derived from human somatic cells.'' Science 318, 1917–1920, 2007.</ref>  
Lin28 is a conserved cytoplasmic protein with an unusual pairing of RNA binding motifs: a cold shock domain and a pair of retroviral type CCHC zinc fingers. It plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, Lin28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. Mammals have two homologs, Lin28a and Lin28b. These two homologs are found from worms to humans.<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><ref>Erica Balzer and Eric G. Moss: ''Localization of the Developmental Timing Regulator Lin28 to mRNP Complexes, P-bodies and Stress Granules.'' In: RNA Biology 4:1, S.16-25, January/February/March 2007.</ref> Lin28a is highly expressed in embryonic stem cells (ESCs) and was shown as one of the four factors that convert fibroblasts into induced pluripotent stem cells.<ref>Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., et al. In: ''Induced pluripotent stem cell lines derived from human somatic cells.'' Science 318, 1917–1920, 2007.</ref>  


== '''Activity''' ==
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>


Line 15: Line 16:


== '''Structure''' ==
== '''Structure''' ==
Lin28 consists of two domains: a cold shock domain and a pair of CCHC zinc fingers.
Both are RNA binding domains. The cold-shock domain (CSD) at the N-terminal part of lin28A interacts with a loop, with a GNGAY motif, of the RNA.
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 than they build a complex with a crystallographic structure together.




Revision as of 22:03, 2 January 2013

Template:Sandbox ESBS 2012

pdb 2cqf protein lin28A

Drag the structure with the mouse to rotate

DescriptionDescription

Lin28 is a conserved cytoplasmic protein with an unusual pairing of RNA binding motifs: a cold shock domain and a pair of retroviral type CCHC zinc fingers. It plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, Lin28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. Mammals have two homologs, Lin28a and Lin28b. These two homologs are found from worms to humans.[1][2] Lin28a is highly expressed in embryonic stem cells (ESCs) and was shown as one of the four factors that convert fibroblasts into induced pluripotent stem cells.[3]

ActivityActivity

At the molecular level, Lin28 acts as a suppressor of let-7 microRNA biogenesis.[4][5][6][7] In the nucleus, Lin28 binds to the primary transcript of let-7 (pri-let-7) and prevents its processing by RNase III DROSHA.[8][9] In the cytoplasm, it interacts with the precursor form of let-7 (pre-let-7) and interferes with pre-let-7 processing. [10][11] Lin28 recruits TUTase 4 (ZCCHC11) to induce oligo-uridylation of pre-let-7, which effectively blocks DICER processing and facilitates degradation of the RNA. [12][13][14] Lin28A is found mostly in the cytoplasmic compartment and acts in concert with TUTase 4.[15]

Let-7 is a key target of Lin28 but there are four additional functions: First, during retinoic-acid-induced neurogliogenesis, Lin28a overexpression altered the expression of several transcription factors involved in early embryonic cell fate decision before any increase in let-7 level was detected. [16] Second, impaired glucose tolerance and insulin resistance were observed in muscle-specific Lin28a knockout mice without significant changes in the let-7 level.[17] Third, Lin28A interacts with mRNAs and cosediments with polysome in sucrose gradient centrifugation.[18] Consistently, several studies reported that Lin28A can bind to and enhance translation of certain mRNAs such as Igf2 in differentiating myoblasts and Oct4 in ESCs.[19][20][21][22]

StructureStructure

Lin28 consists of two domains: a cold shock domain and a pair of CCHC zinc fingers. Both are RNA binding domains. The cold-shock domain (CSD) at the N-terminal part of lin28A interacts with a loop, with a GNGAY motif, of the RNA. 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 in the zinc finger motif. [23]

When lin28A interacts with let-7 than they build a complex with a crystallographic structure together.


ApplicationsApplications

ReferencesReferences

  1. ↑ 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
  2. ↑ Erica Balzer and Eric G. Moss: Localization of the Developmental Timing Regulator Lin28 to mRNP Complexes, P-bodies and Stress Granules. In: RNA Biology 4:1, S.16-25, January/February/March 2007.
  3. ↑ Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., et al. In: Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920, 2007.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ Viswanathan, S.R., Daley, G.Q., and Gregory, R.I. In: Selective blockade of microRNA processing by Lin28. Science 320, 97–100, 2008.
  8. ↑ 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.
  9. ↑ Viswanathan, S.R., Daley, G.Q., and Gregory, R.I. In: Selective blockade of microRNA processing by Lin28. Science 320, 97–100, 2008.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ Balzer, E., Heine, C., Jiang, Q., Lee, V.M., and Moss, E.G. In: LIN28 alters cell fate succession and acts independently of the let-7 microRNA during neurogliogenesis in vitro. Development 137, S.891–900, 2010.
  17. ↑ Zhu, H., Shyh-Chang, N., Segre , A.V., Shinoda, G., Shah, S.P., Einhorn, W.S., Takeuchi, A., Engreitz, J.M., Hagan, J.P., Kharas, M.G., et al; DIAGRAM Consortium; MAGIC Investigators. In: The Lin28/let-7 axis regulates glucose metabolism. Cell 147, S.81–94, 2011.
  18. ↑ Erica Balzer and Eric G. Moss: Localization of the Developmental Timing Regulator Lin28 to mRNP Complexes, P-bodies and Stress Granules. In: RNA Biology 4:1, S.16-25, January/February/March 2007.
  19. ↑ Polesskaya, A., Cuvellier, S., Naguibneva, I., Duquet, A., Moss, E.G., and Harel-Bellan, A. In: Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency. Genes Dev. 21, 1125–1138, 2007.
  20. ↑ Qiu, C., Ma, Y., Wang, J., Peng, S., and Huang, Y. In: Lin28-mediated post-transcriptional regulation of Oct4 expression in human embryonic stem cells. Nucleic Acids Res. 38, S.1240–1248, 2010.
  21. ↑ Xu, B., and Huang, Y. In: Histone H2a mRNA interacts with Lin28 and contains a Lin28-dependent posttranscriptional regulatory element. Nucleic Acids Res. 37, S.4256–4263, 2009.
  22. ↑ Xu, B., Zhang, K., and Huang, Y. In: Lin28 modulates cell growth and associates with a subset of cell cycle regulator mRNAs in mouse embryonic stem cells. RNA 15, S.357–361, 2009.
  23. ↑ 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

ContributorsContributors

Katrin Frohnmüller, Teresa Wiese

pdb 2li8 crystall structure lin28A/let-7

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Teresa Wiese, Katrin Frohnmüller
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=Sandbox_Reserved_718&oldid=1644997"