Merel Derksen

Foto Merel
M.Derksen@ncmls.ru.nl
+31(0)24 3616748
Lab 6.15

Research

RNase MRP is an essential endoribonuclease found in all eukaryotes. RNase MRP is a ribonucleoprotein (RNP) complex that accumulates in the nucleoli of eukaryotic cells. Ten different proteins and a single RNA component have been found to be associated with the human RNase MRP. Mutations in the RNA component cause cartilage hair hypoplasia (CHH), a rare pleiotropic disease. CHH is characterized by a short stature and hypoplastic hair. Moreover, immune deficiencies, Hirschprung disease and an increased risk for developing certain types of cancer are observed in CHH patients.

Over the years many efforts have been taken to identify RNase MRP substrates. So far, the precursor of ribosomal RNA, cyclin B2 mRNA and viperin mRNA have been proposed as substrates, but evidence for cyclin B2 mRNA and pre-rRNA is ambiguous. The identification of substrates is complicated by the fact that RNase MRP is structurally highly similar to RNase P, another essential endoribonuclease. Human RNase MRP and RNase P have distinct RNA components but share all their protein subunits and therefore it is difficult to isolate RNase MRP and RNase P separately.

The goals of my project are to further characterize the molecular composition of the human RNase MRP/P complexes and to identify RNase MRP substrates. This will lead to increased knowledge of the biochemical function and pathophysiological aspects of RNase MRP. The methods applied in this project include, but are not restricted to RNA tagging, tandem affinity purification, SILAC and UV-cross linking and (high-throughput) analysis of cDNAs (CRAC).

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