Developmental aspects of uridine addition within mitochondrial transcripts of Trypanosoma brucei

1988 ◽  
Vol 8 (3) ◽  
pp. 1259-1265
Author(s):  
J E Feagin ◽  
K Stuart
Keyword(s):  
Life Cycle ◽  
Cytochrome Oxidase ◽  
Trypanosoma Brucei ◽  
Cytochrome B ◽  
Respiratory System ◽  
Life Cycle Stage ◽  
Stage Specificity ◽  
Life Cycle Stages ◽  
Mitochondrial Transcripts ◽  
Cytochrome Oxidase Ii

The mitochondrial respiratory system is absent in slender bloodstream forms of Trypanosoma brucei, incomplete in stumpy bloodstream forms, and complete in procyclic (insect) forms. The steady-state abundance of transcripts of some mitochondrially encoded components of the respiratory system correlates with its differential expression in different life cycle stages. Recently, it was reported that uridines which are not encoded in the genome are added to cytochrome b and cytochrome oxidase II transcripts. We now report that the (U)+ transcripts of both genes are found in procyclic forms and to some degree in stumpy forms but are absent in slender forms. The uridine additions to cytochrome oxidase II correct a frameshift in the gene and presumably allow production of a full-length protein, whereas those added to cytochrome b create an in-frame AUG which extends the N terminus of the predicted protein by 20 amino acids. The stage specificity of uridine additions to these transcripts thus reflects the life cycle stage during which the protein products would be used. Transcripts of MURF2, a gene of unknown function, have additional uridines in both slender and procyclic forms which create two in-frame AUGs. MURF2 transcripts additionally differ from the DNA sequence in ways which cannot be explained by uridine addition alone, implying that other processes alter these transcripts.

scholarly journals Developmental aspects of uridine addition within mitochondrial transcripts of Trypanosoma brucei.

1988 ◽  
Vol 8 (3) ◽  
pp. 1259-1265 ◽  
Author(s):  
J E Feagin ◽  
K Stuart
Keyword(s):  
Life Cycle ◽  
Cytochrome Oxidase ◽  
Trypanosoma Brucei ◽  
Cytochrome B ◽  
Respiratory System ◽  
Life Cycle Stage ◽  
Stage Specificity ◽  
Life Cycle Stages ◽  
Mitochondrial Transcripts ◽  
Cytochrome Oxidase Ii

The mitochondrial respiratory system is absent in slender bloodstream forms of Trypanosoma brucei, incomplete in stumpy bloodstream forms, and complete in procyclic (insect) forms. The steady-state abundance of transcripts of some mitochondrially encoded components of the respiratory system correlates with its differential expression in different life cycle stages. Recently, it was reported that uridines which are not encoded in the genome are added to cytochrome b and cytochrome oxidase II transcripts. We now report that the (U)+ transcripts of both genes are found in procyclic forms and to some degree in stumpy forms but are absent in slender forms. The uridine additions to cytochrome oxidase II correct a frameshift in the gene and presumably allow production of a full-length protein, whereas those added to cytochrome b create an in-frame AUG which extends the N terminus of the predicted protein by 20 amino acids. The stage specificity of uridine additions to these transcripts thus reflects the life cycle stage during which the protein products would be used. Transcripts of MURF2, a gene of unknown function, have additional uridines in both slender and procyclic forms which create two in-frame AUGs. MURF2 transcripts additionally differ from the DNA sequence in ways which cannot be explained by uridine addition alone, implying that other processes alter these transcripts.

Diverse patterns of expression of the cytochrome c oxidase subunit I gene and unassigned reading frames 4 and 5 during the life cycle of Trypanosoma brucei

1985 ◽  
Vol 5 (11) ◽  
pp. 3041-3047
Author(s):  
D P Jasmer ◽  
J E Feagin ◽  
K Stuart
Keyword(s):  
Life Cycle ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Trypanosoma Brucei ◽  
Protein Coding ◽  
Oxidase Subunit ◽  
Life Cycle Stages ◽  
Multiple Processes ◽  
Mitochondrial Transcripts ◽  
Reading Frames

Transcription of a maxicircle segment from Trypanosoma brucei 164 that contains nucleotide (nt) sequences corresponding to cytochrome c oxidase subunit I (COI) and unassigned reading frames (URFs) 4 and 5 of other mitochondrial systems was investigated. Two major transcripts that differ in size by ca. 200 nt map to each of the COI and URF4 genes, while a single major transcript maps to URF5. In total RNA, the larger COI transcript is more abundant in procyclic forms (PFs) than in bloodstream forms (BFs), the smaller COI and both URF4 transcripts have similar abundances in both forms, and the single URF5 transcript is more abundant in BF than PF. These patterns of expression differ in poly(A)+ RNA as a result of a higher proportion of poly(A)+ mitochondrial transcripts in PFs than in BFs. In addition, small (300- to 500-nt) RNAs that are transcribed from C-rich sequences located between putative protein-coding genes also exhibit diverse patterns of expression between life cycle stages and differences in polyadenylation in PFs compared with BFs. These observations suggest that multiple processes regulate the differential expression of mitochondrial genes in T. brucei.

scholarly journals Diverse patterns of expression of the cytochrome c oxidase subunit I gene and unassigned reading frames 4 and 5 during the life cycle of Trypanosoma brucei.

1985 ◽  
Vol 5 (11) ◽  
pp. 3041-3047 ◽  
Author(s):  
D P Jasmer ◽  
J E Feagin ◽  
K Stuart
Keyword(s):  
Life Cycle ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Trypanosoma Brucei ◽  
Protein Coding ◽  
Oxidase Subunit ◽  
Life Cycle Stages ◽  
Multiple Processes ◽  
Mitochondrial Transcripts ◽  
Reading Frames

Transcription of a maxicircle segment from Trypanosoma brucei 164 that contains nucleotide (nt) sequences corresponding to cytochrome c oxidase subunit I (COI) and unassigned reading frames (URFs) 4 and 5 of other mitochondrial systems was investigated. Two major transcripts that differ in size by ca. 200 nt map to each of the COI and URF4 genes, while a single major transcript maps to URF5. In total RNA, the larger COI transcript is more abundant in procyclic forms (PFs) than in bloodstream forms (BFs), the smaller COI and both URF4 transcripts have similar abundances in both forms, and the single URF5 transcript is more abundant in BF than PF. These patterns of expression differ in poly(A)+ RNA as a result of a higher proportion of poly(A)+ mitochondrial transcripts in PFs than in BFs. In addition, small (300- to 500-nt) RNAs that are transcribed from C-rich sequences located between putative protein-coding genes also exhibit diverse patterns of expression between life cycle stages and differences in polyadenylation in PFs compared with BFs. These observations suggest that multiple processes regulate the differential expression of mitochondrial genes in T. brucei.

Guide RNAs for transcripts with developmentally regulated RNA editing are present in both life cycle stages of Trypanosoma brucei

1992 ◽  
Vol 12 (5) ◽  
pp. 2043-2049
Author(s):  
D J Koslowsky ◽  
G R Riley ◽  
J E Feagin ◽  
K Stuart
Keyword(s):  
Cytochrome Oxidase ◽  
Trypanosoma Brucei ◽  
Rna Editing ◽  
Developmental Regulation ◽  
Life Forms ◽  
Developmentally Regulated ◽  
Guide Rnas ◽  
Life Cycle Stages ◽  
Mitochondrial Transcripts ◽  
Atpase 6

RNA editing of several mitochondrial transcripts in Trypanosoma brucei is developmentally regulated. The cytochrome b and cytochrome oxidase II mRNAs are edited in procyclic-form parasites but are primarily unedited in bloodstream forms. The latter forms lack the mitochondrial respiratory system present in procyclic forms. Editing of the NADH dehydrogenase 7 (ND7) and ND8 transcripts is also developmentally regulated but occurs preferentially in bloodstream forms. Other transcripts, cytochrome oxidase III and ATPase 6, are edited in both life forms. We have identified many minicircle-encoded guide RNAs (gRNAs) for ATPase 6, ND7, and ND8. The characteristics of these gRNAs reveal how extensively edited RNA can be edited in the 3'-to-5' direction. Northern (RNA) blot and primer extension analyses indicate that gRNAs for transcripts whose editing is developmentally regulated are present in both procyclic and bloodstream form parasites. These results suggest that the developmental regulation of editing in these transcripts is not controlled by the presence or absence of gRNAs.

scholarly journals Guide RNAs for transcripts with developmentally regulated RNA editing are present in both life cycle stages of Trypanosoma brucei.

1992 ◽  
Vol 12 (5) ◽  
pp. 2043-2049 ◽  
Author(s):  
D J Koslowsky ◽  
G R Riley ◽  
J E Feagin ◽  
K Stuart
Keyword(s):  
Cytochrome Oxidase ◽  
Trypanosoma Brucei ◽  
Rna Editing ◽  
Developmental Regulation ◽  
Life Forms ◽  
Developmentally Regulated ◽  
Guide Rnas ◽  
Life Cycle Stages ◽  
Mitochondrial Transcripts ◽  
Atpase 6

RNA editing of several mitochondrial transcripts in Trypanosoma brucei is developmentally regulated. The cytochrome b and cytochrome oxidase II mRNAs are edited in procyclic-form parasites but are primarily unedited in bloodstream forms. The latter forms lack the mitochondrial respiratory system present in procyclic forms. Editing of the NADH dehydrogenase 7 (ND7) and ND8 transcripts is also developmentally regulated but occurs preferentially in bloodstream forms. Other transcripts, cytochrome oxidase III and ATPase 6, are edited in both life forms. We have identified many minicircle-encoded guide RNAs (gRNAs) for ATPase 6, ND7, and ND8. The characteristics of these gRNAs reveal how extensively edited RNA can be edited in the 3'-to-5' direction. Northern (RNA) blot and primer extension analyses indicate that gRNAs for transcripts whose editing is developmentally regulated are present in both procyclic and bloodstream form parasites. These results suggest that the developmental regulation of editing in these transcripts is not controlled by the presence or absence of gRNAs.

scholarly journals The Open Innovation Model of Coaching Interaction in Organisations for Sustainable Performance within the Life Cycle

2018 ◽  
Vol 10 (10) ◽  
pp. 3516 ◽  
Author(s):  
Angelina Roša (Rosha) ◽  
Natalja Lace
Keyword(s):  
Life Cycle ◽  
Open Innovation ◽  
Growth And Development ◽  
Driving Forces ◽  
Life Cycle Stage ◽  
Sustainable Growth ◽  
Business World ◽  
Sustainable Performance ◽  
Life Cycle Stages ◽  
Innovation Model

Organizations need innovation to be competitive and sustainable on their marketplace. Sustainable performance is an important precondition for growth and development. In spite of a body of literature, non-financial factors of sustainable performance remain an open issue. Coaching has gained considerable attention in the business world for its impact on sustainable performance. The current research investigates the use of coaching interaction to facilitate organizational sustainable growth and development in the context of Miller and Friesen’s five stage life-cycle model. The expert opinion survey is chosen as a central method of research. The questionnaire is developed on the literature review that is focused on the drivers for sustainable development throughout the life cycle, and the features of coaching that accelerate these driving forces. Fifteen experts took part in the survey conducted from November 2017 to January 2018. The results are estimated by considering the competence coefficient for each expert. The findings led to creation of an open innovation model, which displays relationships between the appropriate coaching forms and types and the organizational life cycle stages. The developed model enables choosing the optimal way of coaching delivery at any life cycle stage. This model is particularly valuable for the coaching support programs.

Is there a decision to make, boss? From understanding SME growth to managing employees' learning preferences

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Steven Tam ◽  
David E. Gray
Keyword(s):  
Life Cycle ◽  
High Growth ◽  
Life Cycle Stage ◽  
Learning Preferences ◽  
Best Interests ◽  
Structured Interviews ◽  
Managerial Decision ◽  
Content Type ◽  
Learning Practices ◽  
Life Cycle Stages

PurposeThis study examines employees' learning preferences in small and medium-sized enterprises (SMEs) at different life-cycle stages.Design/methodology/approachThe study has two phases. Phase I classified a sample of 30 Hong Kong SMEs into three different life-cycle stages (inception, high growth or maturity). Phase II then explored/compared their employees' learning practices in terms of importance using a mixed-method design through an online learning questionnaire followed by face-to-face semi-structured interviews.FindingsBased on a list of 32 learning practices common to SME workplaces, the study identified how SME employees perceive the importance of a learning practice. The top 5 and the bottom 5 learning practices in SMEs across life-cycle stages are presented to promote best interests for SME executives.Research limitations/implicationsWhile SME learning is highly varied, this study sheds light on some traceable context about it as an SME grows. Similar studies with additional SMEs, including SMEs in other locations, are encouraged to strengthen the findings.Practical implicationsThe findings help SME executives understand what learning practices are most important (or least important) for their employees, given the life-cycle stage of the firm. Aligning a business with employees' learning preferences in a timely fashion is a managerial decision to be made for driving organizational effectiveness.Originality/valueIt is among the first studies connecting employee learning in SMEs and organizational life cycle to address a critical but missing inquiry.

scholarly journals Identification of an antiretroviral small molecule that appears to be a host-targeting inhibitor of HIV-1 assembly.

2020 ◽  
Author(s):  
Jonathan C. Reed ◽  
Dennis Solas ◽  
Anatoliy Kitaygorodskyy ◽  
Beverly Freeman ◽  
Dylan T. B. Ressler ◽  
...  
Keyword(s):  
Life Cycle ◽  
Virus Production ◽  
Life Cycle Stage ◽  
Multidrug Resistant ◽  
Capsid Assembly ◽  
Resistance Mutations ◽  
Life Cycle Stages ◽  
Human T Cell ◽  
Gag Assembly ◽  
Hiv 1

Given the projected increase in multidrug resistant HIV-1, there is an urgent need for development of antiretrovirals that act on virus life-cycle stages not targeted by drugs currently in use. Host-targeting compounds are of particular interest because they can offer a high barrier to resistance. Here we report identification of two related small molecules that inhibit HIV-1 late events, an HIV-1 life cycle stage for which potent and specific inhibitors are lacking. This chemotype was discovered using cell-free protein synthesis and assembly systems that recapitulate intracellular host-catalyzed viral capsid assembly pathways. These compounds inhibit replication of HIV-1 in human T cell lines and PBMCs and are effective against a primary isolate. They reduce virus production, likely by inhibiting a post-translational step in HIV-1 Gag assembly. Notably, the compound colocalizes with HIV-1 Gag in situ; however, unexpectedly, selection experiments failed to identify compound-specific resistance mutations in gag or pol, even though known resistance mutations developed upon parallel nelfinavir selection. Thus, we hypothesized that instead of binding to Gag directly, these compounds localize to assembly intermediates, the intracellular multiprotein complexes containing Gag and host factors that form during immature HIV-1 capsid assembly. Indeed, imaging of infected cells shows compound colocalized with two host enzymes found in assembly intermediates, ABCE1 and DDX6, but not two host proteins found in other complexes. While the exact target and mechanism of action of this chemotype remain to be determined, these findings suggest that these compounds represent first-in-class, host-targeting inhibitors of intracellular events in HIV-1 assembly. IMPORTANCE The success of antiretroviral treatment for HIV-1 is at risk of being undermined by the growing problem of drug resistance. Thus, there is a need to identify antiretrovirals that act on viral life cycle stages not targeted by drugs in use, such as the events of HIV-1 Gag assembly. To address this gap, we developed a compound screen that recapitulates the intracellular events of HIV-1 assembly, including viral-host interactions that promote assembly. This effort led to identification of a new chemotype that inhibits HIV-1 replication at nanomolar concentrations, likely by acting on assembly. This compound colocalized with Gag and two host enzymes that facilitate capsid assembly. However, resistance selection did not result in compound-specific mutations in gag, suggesting that the chemotype does not directly target Gag. We hypothesize that this chemotype represents a first-in-class inhibitor of virus production that acts by targeting a viral-host complex important for HIV-1 Gag assembly.

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