Proinsulin is encoded by an RNA splice variant in human blood myeloid cells

Narendran, Parth, Neale, Alana M., Lee, Bo Han, Ngui, Katrina, Steptoe, Raymond J., Morahan, Grant, Madsen, Ole, Dromey, James A., Jensen, Kent P. and Harrison, Leonard C. (2006) Proinsulin is encoded by an RNA splice variant in human blood myeloid cells. Proceedings of The National Academy of Sciences of The United States of America, 103 44: 16430-16435. doi:10.1073/pnas.0607380103


Author Narendran, Parth
Neale, Alana M.
Lee, Bo Han
Ngui, Katrina
Steptoe, Raymond J.
Morahan, Grant
Madsen, Ole
Dromey, James A.
Jensen, Kent P.
Harrison, Leonard C.
Title Proinsulin is encoded by an RNA splice variant in human blood myeloid cells
Journal name Proceedings of The National Academy of Sciences of The United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2006
Sub-type Article (original research)
DOI 10.1073/pnas.0607380103
Volume 103
Issue 44
Start page 16430
End page 16435
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2006
Language eng
Subject CX
320202 Cellular Immunology
730102 Immune system and allergy
Abstract Genes for peripheral tissue-restricted self-antigens are expressed in thymic and hematopoietic cells. In thymic medullary epithelial cells, self-antigen expression imposes selection on developing autoreactive T cells and regulates susceptibility to autoimmune disease in mouse models. Less is known about the role of self-antigen expression by hematopoietic cells. Here we demonstrate that one of the endocrine self-antigens expressed by human blood myeloid cells, proinsulin, is encoded by an RNA splice variant. The surface expression of immunoreactive proinsulin was significantly decreased after transfection of monocytes with small interfering RNA to proinsulin. Furthermore, analogous to proinsulin transcripts in the thymus, the abundance of the proinsulin RNA splice variant in blood cells corresponded with the length of the variable number of tandem repeats 5' of the proinsulin gene, known to be associated with type 1 diabetes susceptibility. Self-antigen expression by peripheral myeloid cells extends the umbrella of immunological self and, by analogy with the thymus, may be implicated in peripheral immune tolerance.
Keyword Immunology
Variable number of tandem repeats
Insulin
Type 1 diabetes
siRNA
Self-antigen
Q-Index Code CX
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 10:42:14 EST