Alternative splicing of a cryptic exon embedded in intron 6 of SMN1 and SMN2.

Satomi Yoshimoto,Naoya Morisada,Kazumoto Iijima,Masafumi Matsuo,Yuko Hamamura,Hisahide Nishio,Kayoko Saito,Ai Shima,Masakazu Shinohara,Ichiro Morioka,Toshio Saito,Mawaddah Ar Rochmah,Poh San Lai,Nur Imma Fatimah Harahap,Hiroyuki Awano

doi:10.1038/hgv.2016.40

Abstract

Both survival of motor neuron (SMN) genes are associated with spinal muscular atrophy; mutations in SMN1 cause the disease, and SMN2 modulates its severity. It is established that different alternative splicing of exon 7 occurs for SMN1 and SMN2, and a cryptic exon was recently found in intron 6 of both genes. Here, we characterize this cryptic exon and clarify its alternative splicing pattern in control and spinal muscular atrophy cells.

Highlights

Both survival of motor neuron (SMN) genes are associated with spinal muscular atrophy; mutations in SMN1 cause the disease, and SMN2 modulates its severity
It is established that different alternative splicing of exon 7 occurs for SMN1 and SMN2, and a cryptic exon was recently found in intron 6 of both genes
In spinal muscular atrophy (SMA), the low levels of FL-SMN protein generated from SMN2 may partially compensate for the lack of SMN1

Summary

DATA REPORT

Satomi Yoshimoto[1,7], Nur Imma Fatimah Harahap[1,7], Yuko Hamamura[1], Mawaddah Ar Rochmah[1], Ai Shima[1], Naoya Morisada[1,2], Masakazu Shinohara[1], Toshio Saito[3], Kayoko Saito[4], Poh San Lai[5], Masafumi Matsuo[6], Hiroyuki Awano[2], Ichiro Morioka[2], Kazumoto Iijima[2] and Hisahide Nishio[1,2]. We characterized the cryptic SMN exon, exon 7a, and clarified its alternative splicing pattern in control and SMA fibroblast cells. We obtained an amplified product from the control fibroblast cells (‘Mock’ in Figure 1c) and SMA fibroblast cells (data not shown), and DNA sequencing revealed that it corresponds to a transcript containing exon 6-exon 7a. This observation confirmed the presence of an alternative transcript with exon 7a in both the control and SMA fibroblasts. (+504) tct aat ttt ttg tat ttt ttt gta aag ACA GGG TTT CAC TGT GTT AGC CAG GAT GGT CTC AAT CTC CTG ACC CCG TGA TCC ACC CGC CTC GGC CTT CCA AGA GAA ATG AAA TTT TTT TAA TGC ACA AAG ATC TGG Ggt aat gtg tac cac (+654)

SMA Control Control fibroblasts fibroblasts WBC

Findings

NOTE ADDED IN PROOF