The role of pre-mRNA splicing in human hereditary diseases

• Název práce v češtině: Role sestřihu pre-mRNA při rozvoji lidských dědičných onemocněních
• Název v anglickém jazyce: The role of pre-mRNA splicing in human hereditary diseases
• Klíčová slova: pre-mRNA sestřih, retinitis pigmentosa, spinal muscular atrophy, sestřihové snRNP
• Klíčová slova anglicky: pre-mRNA splicing, retinitis pigmentosa, spinal muscular atrophy, spliceosomal snRNP
• Akademický rok vypsání: 2018/2019
• Typ práce: rigorózní práce
• Jazyk práce: angličtina
• Ústav: Katedra genetiky a mikrobiologie (31-140)
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 19.12.2018
• Datum zadání: 19.12.2018
• Datum potvrzení stud. oddělením: 11.01.2019
• Datum odevzdání elektronické podoby: 19.12.2018
• Datum proběhlé obhajoby: 24.01.2019

Předběžná náplň práce v anglickém jazyce

Pre-mRNA splicing is one of the key steps of gene expression during which non-coding sequences - introns - are removed and protein coding sequences - exons - spliced together to form mature mRNA. This process is catalyzed by a huge ribonucleoprotein complex called the spliceosome. The spliceosome is built de novo from basic building blocks, small nuclear ribonucleoproteins (snRNPs), on each intron to be spliced. During splicing, snRNPs undergo extensive rearrangements and must be recycled into active form before next round of splicing.
Surprisingly, mutations in several snRNP specific proteins lead to human hereditary disease retinitis pigmentosa (RP). The patients carrying an RP mutation gradually loose their photoreceptors, which results in lost of peripheral vision, night blindness and eventually total loss of sight. Anna Malinová will focus on snRNP assembly and recycling and analyze how RP-specific mutations affect formation of splicing machinery, namely tri-snRNP and spliceosome formation. She will take advantage of the fact that all the RP specific mutations in snRNP proteins are dominant and express different mutant either in culture cells or in photoreceptors isolated from chicken embryo retina. In addition, Anna will study the SMN protein,whose mutation causes degeneration of motor neurons resulting in spinal muscular atrophy. She will analyze SMN role in the cell nucleus and test the hypothesis that nuclear SMN is important surveillance factor in snRNP assembly.