mRNA export in ME

DNA is transcribed into pre-mRNAs.

mRNAs are packaged into pre-messenger ribonucleoproteins (pre-mRNPs).

Pre-mRNPs are spliced into mature mRNPs.

mRNPs are exported out of the nucleus through the nuclear pore complex (NPC).

SUN1 (=UNC84) is a nuclear envelope protein.

SYNE proteins (nesprins) are part of a network that connects the nuclear envelope to the cytoskeleton.

NXF1 is an export factor.

NUP153 is one of several nucleoporins.

SUN1 recruits NFX1-containing mRNPs onto the nuclear envelope and hands them over to NUP153 (1).





Figure from: Li and Noegel: Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export. Nucleic Acids Research 2015, 43, 20, 9874-9888 (1).

The gene SUN1 is hypomethylated in CD4⁺  T cells (2), and in peripheral blood mononuclear cells (PBMC) from ME patients in two studies (3, 4).

The hypomethylation is related to quality of life in ME patients (table S7 in ref 4).

SYNE1 and SYNE2 are hypermethylated in ME patients (3, 4). The SYNE2 hypermethylation (body and TSS1500) is related to quality of life in ME patients (table S7 in ref 4).

SYNE2 is differentially methylated in ME subtypes (no 73 and no 1732 in table S3 in ref 5).

NXF1 is hypermethylated (TSS1500) in ME patients and the methylation is related to quality of life (table S7 in ref 4).

NXF1 gene expression is up-regulated (adjustet p-value = 0,0682) in whole blood from adolescent CFS patients (6).

References:

1. Li and Noegel: Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export. Nucleic Acids Research 2015, 43, 20, 9874-9888 (1)
2. Brenu et al: Methylation Profile of CD4⁺  T cells in CFS/ME. J. Clin Cell Immunol 2014, 5, 3.
3. de Vega et al: DNA methylation Modifications associated with CFS. PlosOne, 2014, 9, 8
4. de Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11
5. de Vega et al: Integration of DNA methylation & health scores identifies subtypes in ME/CFS. Epigenomics 2018, 10, 5.
6. Nguyen et al: Whole blood gene expression in adolescent CFS: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. J Trans Med, 2017, 15, 102.