TY  - JOUR
A1  - Adamla, Frauke
A1  - Ignatova, Zoya
T1  - Somatic expression of unc-54 and vha-6 mRNAs declines but not pan-neuronal rgef-1 and unc-119 expression in aging Caenorhabditis elegans
JF  - Scientific reports
N2  - Aging is a highly controlled biological process characterized by a progressive deterioration of various cellular activities. One of several hallmarks of aging describes a link to transcriptional alteration, suggesting that it may impact the steady-state mRNA levels. We analyzed the mRNA steady-state levels of polyCAG-encoding transgenes and endogenous genes under the control of well-characterized promoters for intestinal (vha-6), muscular (unc-54, unc-15) and pan-neuronal (rgef-1, unc-119) expression in the nematode Caenorhabditis elegans. We find that there is not a uniform change in transcriptional profile in aging, but rather a tissue-specific difference in the mRNA levels of these genes. While levels of mRNA in the intestine (vha-6) and muscular (unc-54, unc-15) cells decline with age, pan-neuronal tissue shows more stable mRNA expression (rgef-1, unc-119) which even slightly increases with the age of the animals. Our data on the variations in the mRNA abundance from exemplary cases of endogenous and transgenic gene expression contribute to the emerging evidence for tissue-specific variations in the aging process.
Y1  - 2015
U6  - https://doi.org/10.1038/srep10692
SN  - 2045-2322
VL  - 5
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Saffert, Paul
A1  - Adamla, Frauke
A1  - Schieweck, Rico
A1  - Atkins, John F.
A1  - Ignatova, Zoya
T1  - An Expanded CAG Repeat in Huntingtin Causes+1 Frameshifting
JF  - The journal of biological chemistry
N2  - Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5 end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1.
KW  - aggregation
KW  - Huntington disease
KW  - translation
KW  - translation regulation
KW  - trinucleotide repeat disease
KW  - frameshifting
KW  - seeding
Y1  - 2016
U6  - https://doi.org/10.1074/jbc.M116.744326
SN  - 0021-9258
SN  - 1083-351X
VL  - 291
SP  - 18505
EP  - 18513
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  -