This leads to global gene expression changes and premature aging.
Berrant splicing of lamin a.
Due to alternative splicing the lamin a gene generates several isoforms including lamin a c c2 and lamin ad10 cau et al.
The lmna gene gives rise to at least three isoforms lamin a c lamin aδ10 as a result of normal alternative splicing regulated by cis and trans acting regulatory factors as well as the 5 and 3 untranslated regions of the gene.
To identify small molecule modulators of aberrant lmna splicing a homogenous assay was constructed in hela cells that used a gfp containing minigene to report on correction of aberrant splicing in lamin a and a rfp dsred2 to report on cell viability uniformity and nonspecific effects on the assay signal.
The two main isoforms lamin a and c are constitutive components of the fibrous nuclear lamina and have diverse physiological roles ranging from.
Aberrant splicing in the lmna gene caused by a novel mutation on the polypyrimidine tract of intron 5.
The occurrence of lamin a aberrant splicing in wild type cells suggests that δ50 lamin a is present in cells from healthy individuals.
Carboni n 1 floris m mateddu a porcu m marrosu g solla e cocco e mura m marini s maioli ma piras r aste r marrosu mg.
The lmna gene gives rise to at least three isoforms lamin a c lamin aδ10 as a result of normal alternative splicing regulated by cis and trans acting regulatory factors as well as the 5 and 3 untranslated regions of the gene.
The two main isoforms lamin a and c are constitutive components of the fibrous nuclear lamina and have diverse physiological roles ranging from.
A well known example is a mutation in lmna which introduces a novel 5 splice site and generates a truncated lamin a protein that impairs nuclear membrane function.
On the other hand the two b type lamins b1.
A truncated protein of the expected molecular weight was detected in wild type cells by antibodies against lamin a and c lamin a c upon extraction of soluble proteins and enrichment for membrane associated.
It has been proposed that a b type lamin gene is the ancestral gene of the lamin family and that lmna may have developed from this gene by the insertion of an extra exon exon 11 during evolution 28 interestingly the insertion of exon 11 nor mally generates lamin a but mis splicing can lead to a product from a cryptic splice site within exon 11.
1a lamin a and lamin c are major components of the nuclear lamina a complex molecular interface located between the inner membrane of the nuclear envelope and chromatin lamins a and c are also distributed throughout the nucleoplasm.
