Search for the Function of NWC, Third Gene Within RAG Locus: Generation and Characterization of NWC-Deficient Mice

Overview

Journal Arch Immunol Ther Exp (Warsz)

Publisher Sciendo

Specialty Allergy & Immunology

Date 2015 Dec 26

PMID 26703212

Citations 1

Authors

Monika Kasztura

Lukasz Sniezewski

Agnieszka Laszkiewicz

Michal Majkowski

Kamil Kobak

Karolina Peczek

Sylwia Janik

Violetta Kapusniak

Arkadiusz Miazek

Malgorzata Cebrat

Pawel Kisielow

Affiliations

Soon will be listed here.

Abstract

NWC is a third gene within recombination activating gene (RAG) locus, which unlike RAG genes is ubiquitously expressed and encodes a unique protein containing three strongly evolutionarily conserved domains not found in any other known protein. To get insight into its function we identified several proteins co-immunoprecipitating with NWC protein and generated new NWC-deficient mice. Here, we present evidence that unlike many other ubiquitously expressed evolutionarily conserved proteins, functional inactivation of NWC does not cause any gross developmental, physiological or reproductive abnormalities and that under physiological conditions NWC may be involved in assembling and functioning of cilia, cell surface organelles found on nearly every eukaryotic cell.

Citing Articles

Lack of NWC protein (c11orf74 homolog) in murine spermatogenesis results in reduced sperm competitiveness and impaired ability to fertilize egg cells in vitro.

Majkowski M, Laszkiewicz A, Sniezewski L, Grzmil P, Pawlicka B, Tomczyk I PLoS One. 2018; 13(12):e0208649.

PMID: 30521625 PMC: 6283527. DOI: 10.1371/journal.pone.0208649.

References

Schatz D, Oettinger M, Baltimore D . The V(D)J recombination activating gene, RAG-1. Cell. 1989; 59(6):1035-48. DOI: 10.1016/0092-8674(89)90760-5. View

Koonin E . Darwinian evolution in the light of genomics. Nucleic Acids Res. 2009; 37(4):1011-34. PMC: 2651812. DOI: 10.1093/nar/gkp089. View

Pitaval A, Christ A, Curtet A, Tseng Q, Thery M . Probing ciliogenesis using micropatterned substrates. Methods Enzymol. 2013; 525:109-30. DOI: 10.1016/B978-0-12-397944-5.00006-7. View

Chatr-Aryamontri A, Breitkreutz B, Oughtred R, Boucher L, Heinicke S, Chen D . The BioGRID interaction database: 2015 update. Nucleic Acids Res. 2014; 43(Database issue):D470-8. PMC: 4383984. DOI: 10.1093/nar/gku1204. View

Kasztura M, Miazek A, Cebrat M, Kisielow P . Identification of a novel protein encoded by third conserved gene within RAG locus. Acta Biochim Pol. 2009; 56(1):177-81. View

Cebrat M, Miazek A, Kisielow P . Identification of a third evolutionarily conserved gene within the RAG locus and its RAG1-dependent and -independent regulation. Eur J Immunol. 2005; 35(7):2230-8. DOI: 10.1002/eji.200526225. View

Laszkiewicz A, Cebrat M, Miazek A, Kisielow P . Complexity of transcriptional regulation within the Rag locus: identification of a second Nwc promoter region within the Rag2 intron. Immunogenetics. 2011; 63(3):183-7. PMC: 3035778. DOI: 10.1007/s00251-011-0511-2. View

White J, Gerdin A, Karp N, Ryder E, Buljan M, Bussell J . Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes. Cell. 2013; 154(2):452-64. PMC: 3717207. DOI: 10.1016/j.cell.2013.06.022. View

Huttlin E, Ting L, Bruckner R, Gebreab F, Gygi M, Szpyt J . The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell. 2015; 162(2):425-440. PMC: 4617211. DOI: 10.1016/j.cell.2015.06.043. View

10.

Ahituv N, Zhu Y, Visel A, Holt A, Afzal V, Pennacchio L . Deletion of ultraconserved elements yields viable mice. PLoS Biol. 2007; 5(9):e234. PMC: 1964772. DOI: 10.1371/journal.pbio.0050234. View

11.

Liao B, Zhang J . Mouse duplicate genes are as essential as singletons. Trends Genet. 2007; 23(8):378-81. DOI: 10.1016/j.tig.2007.05.006. View

12.

Amsterdam A, Nissen R, Sun Z, Swindell E, Farrington S, Hopkins N . Identification of 315 genes essential for early zebrafish development. Proc Natl Acad Sci U S A. 2004; 101(35):12792-7. PMC: 516474. DOI: 10.1073/pnas.0403929101. View

13.

Laszkiewicz A, Sniezewski L, Kasztura M, Bzdzion L, Cebrat M, Kisielow P . Bidirectional activity of the NWC promoter is responsible for RAG-2 transcription in non-lymphoid cells. PLoS One. 2012; 7(9):e44807. PMC: 3439442. DOI: 10.1371/journal.pone.0044807. View

14.

Satir P, Christensen S . Overview of structure and function of mammalian cilia. Annu Rev Physiol. 2006; 69:377-400. DOI: 10.1146/annurev.physiol.69.040705.141236. View

15.

Laszkiewicz A, Bzdzion L, Kasztura M, Sniezewski L, Janik S, Kisielow P . Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter. PLoS One. 2014; 9(9):e106927. PMC: 4157847. DOI: 10.1371/journal.pone.0106927. View

16.

Hao L, Scholey J . Intraflagellar transport at a glance. J Cell Sci. 2009; 122(Pt 7):889-92. PMC: 2720924. DOI: 10.1242/jcs.023861. View

17.

Oettinger M, Schatz D, Gorka C, Baltimore D . RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990; 248(4962):1517-23. DOI: 10.1126/science.2360047. View

18.

Cebrat M, Cebula A, Laszkiewicz A, Kasztura M, Miazek A, Kisielow P . Mechanism of lymphocyte-specific inactivation of RAG-2 intragenic promoter of NWC: implications for epigenetic control of RAG locus. Mol Immunol. 2008; 45(8):2297-306. DOI: 10.1016/j.molimm.2007.11.009. View

19.

Jordan I, Rogozin I, Wolf Y, Koonin E . Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res. 2002; 12(6):962-8. PMC: 1383730. DOI: 10.1101/gr.87702. View