The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells

Jung Min Park, Matthew J. Kohn, Monique W. Bruinsma, Claire Vech, Robert V. Intine, Stacy Fuhrmann, Alex Grinberg, Ipsita Mukherjee, Paul E. Love, Minoru Ko, Melvin L. DePamphilis, Richard J. Maraia

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The La protein is a target of autoantibodies in patients suffering from Sjögren's syndrome, systemic lupus erythematosus, and neonatal lupus. Ubiquitous in eukaryotes, La functions as a RNA-binding protein that promotes the maturation of tRNA precursors and other nascent transcripts synthesized by RNA polymerase III as well as other noncoding RNAs. La also associates with a class of mRNAs that encode ribosome subunits and precursors to snoRNAs involved in ribosome biogenesis. Thus, it was surprising that La is dispensable in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, the organisms from which it has been characterized most extensively. To determine whether La is essential in mammals and if so, at which developmental stage it is required, mice were created with a disrupted La gene, and the offspring from La +/- intercrosses were analyzed. La-/- offspring were detected at the expected frequency among blastocysts prior to implantation, whereas no nullizygotes were detected after implantation, indicating that La is required early in development. Blastocysts derived from La+/- intercrosses yielded 38 La+/+ and La+/- embryonic stem (ES) cell lines but no La-/- ES cell lines, suggesting that La contributes a critical function toward the establishment or survival of ES cells. Consistent with this, La-/- blastocyst outgrowths revealed loss of the inner cell mass (ICM). The results indicate that in contrast to the situation in yeasts, La is essential in mammals and is one of a limited number of genes required as early as the development of the ICM.

Original languageEnglish
Pages (from-to)1445-1451
Number of pages7
JournalMolecular and Cellular Biology
Volume26
Issue number4
DOIs
Publication statusPublished - 2006 Feb
Externally publishedYes

Fingerprint

RNA-Binding Proteins
Blastocyst
Embryonic Stem Cells
Mammals
Yeasts
Small Nucleolar RNA
RNA Polymerase III
Ribosome Subunits
Cell Line
Untranslated RNA
Schizosaccharomyces
RNA Precursors
Eukaryota
Ribosomes
Psychological Stress
Systemic Lupus Erythematosus
Autoantibodies
Genes
Saccharomyces cerevisiae
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells. / Park, Jung Min; Kohn, Matthew J.; Bruinsma, Monique W.; Vech, Claire; Intine, Robert V.; Fuhrmann, Stacy; Grinberg, Alex; Mukherjee, Ipsita; Love, Paul E.; Ko, Minoru; DePamphilis, Melvin L.; Maraia, Richard J.

In: Molecular and Cellular Biology, Vol. 26, No. 4, 02.2006, p. 1445-1451.

Research output: Contribution to journalArticle

Park, JM, Kohn, MJ, Bruinsma, MW, Vech, C, Intine, RV, Fuhrmann, S, Grinberg, A, Mukherjee, I, Love, PE, Ko, M, DePamphilis, ML & Maraia, RJ 2006, 'The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells', Molecular and Cellular Biology, vol. 26, no. 4, pp. 1445-1451. https://doi.org/10.1128/MCB.26.4.1445-1451.2006
Park, Jung Min ; Kohn, Matthew J. ; Bruinsma, Monique W. ; Vech, Claire ; Intine, Robert V. ; Fuhrmann, Stacy ; Grinberg, Alex ; Mukherjee, Ipsita ; Love, Paul E. ; Ko, Minoru ; DePamphilis, Melvin L. ; Maraia, Richard J. / The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 4. pp. 1445-1451.
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AU - Intine, Robert V.

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