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Hebert, M. D.

Publications and source records attributed to Hebert, M. D..

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Regulatory RNPs: A novel class of ribonucleoproteins that contribute to ribosome heterogeneity

Ribonucleoproteins (RNPs), which are comprised of non-coding RNA and associated proteins, are involved in essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal body-specific RNP (scaRNP), which contributes to the biogenesis of small nuclear RNPs (snRNPs) that are central components of the spliceosome. Interestingly, three scaRNAs are internally processed, generating stable nucleolus-enriched RNAs of unknown function. Here we provide evidence that these RNAs become part of novel RNPs we term regulatory RNPs (regRNPs). We postulate that regRNPs can impact rRNA modifications via interactions with the guide RNA component of small nucleolar RNPs (snoRNPs). Most modifications within rRNA (predominantly pseudouridylation and ribose 2-O-methylation) are conducted by snoRNPs, and we hypothesize that the activity of at least some of these snoRNPs is under the control of regRNPs. Ribosome heterogeneity leading to specialized ribosomes is an exciting emerging concept. Because modifications within rRNA can vary in different physiological or pathological situations, rRNA modifications are thought to be the major source of ribosome heterogeneity. Our identification of regRNPs thus provides important and timely insight into how ribosome heterogeneity may be accomplished. This work also provides additional functional connections between the Cajal body and the nucleolus.\n\nSummary StatementProcessed scaRNAs give rise to a novel regulatory RNP which regulates the modification of ribosomal RNA. These findings provide insight into the mechanisms governing ribosome heterogeneity.

molecular biology

Functional Characterization of the Morpheus Gene Family

DATA ACCESSThe cDNA sequences reported in this paper have been deposited in the GenBank database (accession numbers): KF175165-KF175225 and BACs accession numbers that are used in this study: AC148621, AC190226, AC097327, AC097332, AC190226, AC097333, AC145401, AC187943, AC166855, AC166597, AC167295, AC235773, AC202644, and AC234805.\n\nABSTRACTThe burst of segmental duplications during human and great ape evolution focuses on a set of \"core\" duplicons encoding great-ape-specific gene families. Characterization of these gene families is complicated by their high copy number, incomplete sequence, and polymorphic nature. We investigate the structure, transcriptional diversity, and protein localization of the nuclear pore complex-interacting protein (NPIP) or Morpheus gene family. The corresponding core, LCRA, encodes one of the most rapidly evolving genes in the human genome; LCRA has expanded to ~20 copies from a single ancestral locus in Old World monkey and is associated with most of the recurrent chromosome 16 microdeletions implicated in autism and mental retardation. Phylogenetic analysis and cDNA sequencing suggest two distinct subfamilies or subtypes, NPIPA and NPIPB. The latter expanded recently within the great apes due to a series of structural changes within the canonical gene structure. Among Old World monkey, we observe a testis-specific pattern of expression that contrasts with the ubiquitous pattern observed among human tissues. This change in the expression profile coincides with the structural events that reshaped the structure and organization of the gene family. Most of the expressed human copies are capable of producing an open reading frame. Immunofluorescence analyses of the morpheus genes showed a primary localization to both the nucleus and its periphery. We show that morpheus genes may be upregulated upon pI:C treatment and find evidence of human autoantibodies produced against the NPIPB protein, raising the possibility that morpheus genes may be related to immune- or autoimmune-related function.

evolutionary biology