Biomedical subjects

A Gregory Matera

Publications and source records attributed to A Gregory Matera.

22 records · Page 2Linked to original sources

PubMed2003

Interaction between the small-nuclear-RNA cap hypermethylase and the spinal muscular atrophy protein, survival of motor neuron.

The biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) requires the cytoplasmic assembly of the Sm-core complex, followed by the hypermethylation of the small nuclear RNA (snRNA) 5' cap. Both the Sm-core complex and the snRNA trimethylguanosine cap are required for the efficient nuclear import of snRNPs. Here, we show that trimethylguanosine synthase 1 (TGS1), the human homologue of the yeast snRNA cap hypermethylase, interacts directly with the survival of motor neuron (SMN) protein. Both proteins are similarly distributed, localizing in the cytoplasm and in nuclear Cajal bodies. The interaction between TGS1 and SMN is disrupted by a mutation in SMN that mimics the predominant isoform of the protein that is expressed in patients with the neurodegenerative disease, spinal muscular atrophy. These data indicate that, in addition to its function in cytoplasmic Sm-core assembly, the SMN protein also functions in the recruitment of the snRNA cap hypermethylase.

Autoantigens↗

PubMed2002

SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta.

The survival of motor neuron (SMN) protein is mutated in patients with spinal muscular atrophy (SMA). SMN is part of a multiprotein complex required for biogenesis of the Sm class of small nuclear ribonucleoproteins (snRNPs). Following assembly of the Sm core domain, snRNPs are transported to the nucleus via importin beta. Sm snRNPs contain a nuclear localization signal (NLS) consisting of a 2,2,7-trimethylguanosine (TMG) cap and the Sm core. Snurportin1 (SPN) is the adaptor protein that recognizes both the TMG cap and importin beta. Here, we report that a mutant SPN construct lacking the importin beta binding domain (IBB), but containing an intact TMG cap-binding domain, localizes primarily to the nucleus, whereas full-length SPN localizes to the cytoplasm. The nuclear localization of the mutant SPN was not a result of passive diffusion through the nuclear pores. Importantly, we found that SPN interacts with SMN, Gemin3, Sm snRNPs and importin beta. In the presence of ribonucleases, the interactions with SMN and Sm proteins were abolished, indicating that snRNAs mediate this interplay. Cell fractionation studies showed that SPN binds preferentially to cytoplasmic SMN complexes. Notably, we found that SMN directly interacts with importin beta in a GST-pulldown assay, suggesting that the SMN complex might represent the Sm core NLS receptor predicted by previous studies. Therefore, we conclude that, following Sm protein assembly, the SMN complex persists until the final stages of cytoplasmic snRNP maturation and may provide somatic cell RNPs with an alternative NLS.

Carrier Proteins↗

PubMed2002

Proteomics: the nucleolus weighs in.

Numerous studies have indicated that the nucleolus is involved in a variety of cellular processes besides its well-known function in ribosome biosynthesis. A recent study describing the nucleolar proteome opens the way to new avenues of research on this important nuclear suborganelle.

Cell Nucleolus↗

PubMed2002

Coilin methylation regulates nuclear body formation.

Cajal bodies (CBs) are nuclear suborganelles involved in biogenesis of small RNAs. Twin structures, called gems, contain high concentrations of the survival motor neurons (SMN) protein complex. CBs and gems often colocalize, and communication between these subdomains is mediated by coilin, the CB marker. Coilin contains symmetrical dimethylarginines that modulate its affinity for SMN, and, thus, localization of SMN complexes to CBs. Inhibition of methylation or mutation of the coilin RG box dramatically decreases binding of coilin to SMN, resulting in gem formation. Coilin is hypomethylated in cells that display gems, but not in those that primarily contain CBs. Likewise, extracts prepared from cells that display gems are less efficient in methylating coilin and Sm constructs in vitro. These results demonstrate that alterations in protein methylation status can affect nuclear organization.

Adenosine↗