HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats.
In the human genome, dinucleotide repeats are common sequence elements of unknown functional significance. Here we demonstrate that CA repeats in intron 13 of the human endothelial nitric oxide synthase (eNOS) gene function as an unusual intronic splicing enhancer, whose activity depends on the CA repeat number. We identify the 65 kDa heterogenous nuclear ribonucleoprotein (hnRNP) L as the major factor that binds specifically and in a length-dependent manner to the CA-repeat enhancer. In addition, we show that hnRNP L functions as a specific activator of eNOS splicing, providing the first evidence for a role of hnRNP L in the regulation of mRNA splicing. We hypothesize that hnRNP L may be involved in the regulation of many other genes containing CA repeats or A/C-rich enhancers.
Hui
Jingyi
J
Institut für Biochemie, Justus-Liebig-Universität Giessen, Heinrich-Buff-Ring 58, D-35392 Giessen, Germany.
Stangl
Karl
K
Lane
William S
WS
Bindereif
Albrecht
A
D002460:Cell Line; D018900:Dinucleotide Repeats / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006367:HeLa Cells; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007438:Introns / Q000235:genetics; D013058:Mass Spectrometry; D008957:Models, Genetic; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011485:Protein Binding / Q000528:radiation effects; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III