{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/2730"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/2730","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"New Roles in RNA Stability and Transcription for the RNA Export Protein, REF/Aly","abstract":"Pre-mRNA processing consists of a series of events including capping, splicing, and polyadenylation, which occur co-transcriptionally, are interdependent, and are coupled to other steps in gene expression including transcription and RNA export. For example, in mammalian cells the TREX (transcription-export) complex is deposited on an mRNA in a splicing-dependent fashion, leading to more efficient mRNA export. In yeast, TREX is additionally implicated in RNA quality control pathways. Using factors derived from the Kaposi’s sarcoma-associated herpesvirus (KSHV), we established a role for the TREX component, REF/Aly, in nuclear RNA stability. We found that REF/Aly is recruited to the KSHV nuclear noncoding PAN RNA by the viral protein, ORF57, and this recruitment correlates with ORF57-mediated stabilization of PAN RNA. Additionally, REF/Aly is sufficient to increase the nuclear abundance and half-life of PAN RNA, but is not sufficient to promote its export. REF/Aly appears to protect the poly(A) tail from deadenylation and REF/Aly-stabilized transcripts are further adenylated over time, consistent with previous reports linking poly(A) tail length with nuclear RNA surveillance and supporting a broader conservation of RNA quality control mechanisms from yeast to human. Pre-mRNA processing is also mechanistically coupled to transcription with RNA pol II serving as a platform to recruit RNA processing factors to nascent transcripts. Using an RNA-Seq approach, we suggest a role for REF/Aly in transcription in addition to its well-defined role in RNA export. RNA-Seq analysis identified a subset of transcripts with decreased expression in both nuclear and cytoplasmic fractions upon REF/Aly knockdown. Interestingly, we find that REF/Aly does not affect the stability of candidate transcripts, however, REF/Aly depletion affects pol II density on target genes, implying a role for REF/Aly in pol II recruitment. Furthermore, REF/Aly binds directly to candidate transcripts, supporting a direct effect of REF/Aly on candidate gene transcription. Our data are consistent with the model that REF/Aly is involved in linking splicing with transcription efficiency. Taken together, our data suggest that the importance of REF/Aly is not limited to RNA export, but that REF/Aly is also critical for gene expression at the level of RNA stability and transcription.","abstract_html":"Pre-mRNA processing consists of a series of events including capping, splicing, and polyadenylation, which occur co-transcriptionally, are interdependent, and are coupled to other steps in gene expression including transcription and RNA export. For example, in mammalian cells the TREX (transcription-export) complex is deposited on an mRNA in a splicing-dependent fashion, leading to more efficient mRNA export. In yeast, TREX is additionally implicated in RNA quality control pathways. Using factors derived from the Kaposi’s sarcoma-associated herpesvirus (KSHV), we established a role for the TREX component, REF/Aly, in nuclear RNA stability. We found that REF/Aly is recruited to the KSHV nuclear noncoding PAN RNA by the viral protein, ORF57, and this recruitment correlates with ORF57-mediated stabilization of PAN RNA. Additionally, REF/Aly is sufficient to increase the nuclear abundance and half-life of PAN RNA, but is not sufficient to promote its export. REF/Aly appears to protect the poly(A) tail from deadenylation and REF/Aly-stabilized transcripts are further adenylated over time, consistent with previous reports linking poly(A) tail length with nuclear RNA surveillance and supporting a broader conservation of RNA quality control mechanisms from yeast to human. Pre-mRNA processing is also mechanistically coupled to transcription with RNA pol II serving as a platform to recruit RNA processing factors to nascent transcripts. Using an RNA-Seq approach, we suggest a role for REF/Aly in transcription in addition to its well-defined role in RNA export. RNA-Seq analysis identified a subset of transcripts with decreased expression in both nuclear and cytoplasmic fractions upon REF/Aly knockdown. Interestingly, we find that REF/Aly does not affect the stability of candidate transcripts, however, REF/Aly depletion affects pol II density on target genes, implying a role for REF/Aly in pol II recruitment. Furthermore, REF/Aly binds directly to candidate transcripts, supporting a direct effect of REF/Aly on candidate gene transcription. Our data are consistent with the model that REF/Aly is involved in linking splicing with transcription efficiency. Taken together, our data suggest that the importance of REF/Aly is not limited to RNA export, but that REF/Aly is also critical for gene expression at the level of RNA stability and transcription.","abstract_has_math":false,"creators":["Stubbs, Sarah Elizabeth Hulsey"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Pfeiffer, Julie K.","Conrad, Nicholas","Green, Carla B.","Fontoura, Beatriz"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-01-05T19:38:00Z","date_published":"2016-01-05T19:38:00Z","updated_at":"2026-07-24T05:52:15Z","subjects":["RNA Transport","RNA-Binding Proteins","Transcription Factors"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["933743774"],"render_values":[{"text":"933743774","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/2730","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Pfeiffer, Julie K.","Conrad, Nicholas","Green, Carla B.","Fontoura, Beatriz"]},{"key":"dc:creator","label":"Author","values":["Stubbs, Sarah Elizabeth Hulsey"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016-01-05T19:38:00Z","2013-12","2013-10-17","December 2013","2016-01-05T19:08:12Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["RNA Transport","RNA-Binding Proteins","Transcription Factors"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/2730","933743774"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Pre-mRNA processing consists of a series of events including capping, splicing, and polyadenylation, which occur co-transcriptionally, are interdependent, and are coupled to other steps in gene expression including transcription and RNA export. For example, in mammalian cells the TREX (transcription-export) complex is deposited on an mRNA in a splicing-dependent fashion, leading to more efficient mRNA export. In yeast, TREX is additionally implicated in RNA quality control pathways. Using factors derived from the Kaposi’s sarcoma-associated herpesvirus (KSHV), we established a role for the TREX component, REF/Aly, in nuclear RNA stability. We found that REF/Aly is recruited to the KSHV nuclear noncoding PAN RNA by the viral protein, ORF57, and this recruitment correlates with ORF57-mediated stabilization of PAN RNA. Additionally, REF/Aly is sufficient to increase the nuclear abundance and half-life of PAN RNA, but is not sufficient to promote its export. REF/Aly appears to protect the poly(A) tail from deadenylation and REF/Aly-stabilized transcripts are further adenylated over time, consistent with previous reports linking poly(A) tail length with nuclear RNA surveillance and supporting a broader conservation of RNA quality control mechanisms from yeast to human. Pre-mRNA processing is also mechanistically coupled to transcription with RNA pol II serving as a platform to recruit RNA processing factors to nascent transcripts. Using an RNA-Seq approach, we suggest a role for REF/Aly in transcription in addition to its well-defined role in RNA export. RNA-Seq analysis identified a subset of transcripts with decreased expression in both nuclear and cytoplasmic fractions upon REF/Aly knockdown. Interestingly, we find that REF/Aly does not affect the stability of candidate transcripts, however, REF/Aly depletion affects pol II density on target genes, implying a role for REF/Aly in pol II recruitment. Furthermore, REF/Aly binds directly to candidate transcripts, supporting a direct effect of REF/Aly on candidate gene transcription. Our data are consistent with the model that REF/Aly is involved in linking splicing with transcription efficiency. Taken together, our data suggest that the importance of REF/Aly is not limited to RNA export, but that REF/Aly is also critical for gene expression at the level of RNA stability and transcription."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["New Roles in RNA Stability and Transcription for the RNA Export Protein, REF/Aly"]}]}],"canonical_facts":{"dc:contributor":["Pfeiffer, Julie K.","Conrad, Nicholas","Green, Carla B.","Fontoura, Beatriz"],"dc:creator":["Stubbs, Sarah Elizabeth Hulsey"],"dc:date":["2016-01-05T19:38:00Z","2013-12","2013-10-17","December 2013","2016-01-05T19:08:12Z"],"dc:description":["Pre-mRNA processing consists of a series of events including capping, splicing, and polyadenylation, which occur co-transcriptionally, are interdependent, and are coupled to other steps in gene expression including transcription and RNA export. For example, in mammalian cells the TREX (transcription-export) complex is deposited on an mRNA in a splicing-dependent fashion, leading to more efficient mRNA export. In yeast, TREX is additionally implicated in RNA quality control pathways. Using factors derived from the Kaposi’s sarcoma-associated herpesvirus (KSHV), we established a role for the TREX component, REF/Aly, in nuclear RNA stability. We found that REF/Aly is recruited to the KSHV nuclear noncoding PAN RNA by the viral protein, ORF57, and this recruitment correlates with ORF57-mediated stabilization of PAN RNA. Additionally, REF/Aly is sufficient to increase the nuclear abundance and half-life of PAN RNA, but is not sufficient to promote its export. REF/Aly appears to protect the poly(A) tail from deadenylation and REF/Aly-stabilized transcripts are further adenylated over time, consistent with previous reports linking poly(A) tail length with nuclear RNA surveillance and supporting a broader conservation of RNA quality control mechanisms from yeast to human. Pre-mRNA processing is also mechanistically coupled to transcription with RNA pol II serving as a platform to recruit RNA processing factors to nascent transcripts. Using an RNA-Seq approach, we suggest a role for REF/Aly in transcription in addition to its well-defined role in RNA export. RNA-Seq analysis identified a subset of transcripts with decreased expression in both nuclear and cytoplasmic fractions upon REF/Aly knockdown. Interestingly, we find that REF/Aly does not affect the stability of candidate transcripts, however, REF/Aly depletion affects pol II density on target genes, implying a role for REF/Aly in pol II recruitment. Furthermore, REF/Aly binds directly to candidate transcripts, supporting a direct effect of REF/Aly on candidate gene transcription. Our data are consistent with the model that REF/Aly is involved in linking splicing with transcription efficiency. Taken together, our data suggest that the importance of REF/Aly is not limited to RNA export, but that REF/Aly is also critical for gene expression at the level of RNA stability and transcription."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/2730","933743774"],"dc:language":["en"],"dc:subject":["RNA Transport","RNA-Binding Proteins","Transcription Factors"],"dc:title":["New Roles in RNA Stability and Transcription for the RNA Export Protein, REF/Aly"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:15Z"}